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Full text of "A treatise on pellagra : for the general practitioner"

"*. 



A TREATISE ON 

PELLAGRA 



Digitized by the Internet Archive 

in 2012 with funding from 

Open Knowledge Commons and Yale University, Cushing/Whitney Medical Library 



http://archive.org/details/treatiseonpellagOOwood 




Gaetano Strombio, the elder, 1782. 
The Greatest Pellagraloger. 



(From a print in the possession of Professor Sarnbon.) 



A TREATISE ON 

PELLAGRA 

FOR THE GENERAL PRACTITIONER 



BY 

EDWARD JENNER WOOD, S.B., M.D. 

CHAIRMAN OF THE PELLAGRA COMMISSION, NORTH CAROLINA BOARD OF HEALTH 

MEMBER OF THE AMERICAN SOCIETY OF TROPICAL MEDICINE ; FELLOW 

OF THE LONDON SOCIETY OF TROPICAL MEDICINE AND HYGIENE ; 

FORMERLY PRESIDENT OF THE MEDICAL SOCIETY OF 

NORTH CAROLINA, ETC. 



WITH THIRTY-EIGHT ILLUSTRATIONS IN TEXT 




NEW YORK AND LONDON 
D. APPLETON AND COMPANY 

1912 , * 



Copyright, 1912, by 
D. APPLETON AND COMPANY 







■ 



- 



Printed in the United States of America 



TO THE MEMORY OF MY FATHER 
THOMAS F. WOOD, M.D., LL.D. 

OP WILMINGTON, NORTH CAROLINA 

IN APPRECIATION OF 

THE WORK DONE BY HIM FOR HIS NATIVE STATE 

IN THE CAUSE OF 

PUBLIC HEALTH 



PREFACE 

The only justification for this book is the fact that when it was 
begun there was not a single treatise on the subject in the English 
language except the short articles in Allbutt's System and the 
Encyclopedia Britannica. The beginning of this book was the trans- 
lation of Tuczek's " Anatom. und pathologisch. Studien ueber die 
Pellagra." As this was not a complete discourse on the subject 
it was necessary to read other works in German, French, and 
Italian. In the five years that have elapsed the number of these 
translations has grown and to the knowledge gleaned from these 
European masters has been added an experience with a large 
number of cases of the disease. During this period there has been 
much written on the subject in this country and the study of the 
disease has been greatly advanced by the establishment of the 
National Pellagra Conference which meets annually. 

It is one of the most interesting chapters in American medical 
history — this appearance of pellagra. It has been given to few 
to see the appearance of an entirely unknown disease on virgin 
soil and to watch the evolution of that disease through all the 
stages of adaptation to a new field. It has been a study of 
great sociological as well as medical importance. 

The medical profession owes a debt of gratitude to George 
H. Searcy of Alabama for his splendid work in the first recog- 
nition of an outbreak of this disease in the home of the Indian 
corn. There is also a debt that cannot soon be discharged to 
J. W. Babcock of South Carolina for his indomitable perse- 
verence in bringing to the attention of the medical profession and 
the national government the outbreak of the greatest scourge 
which has yet afflicted the American people ; and to him is also 
due the great credit for the founding of the National Pellagra 
Conference which is destined to be one of the most important 
medical and public health organizations in the country. 



viii PREFACE 

Through the outbreak of pellagra in the United States many 
have learned the great importance of that great conservator of 
human life, the United States Public Health and Marine Hos- 
pital Service, while others have for the first time learned to 
appreciate the greatest medical library in the whole world, that 
of the Surgeon-General. 

It has been attempted in this volume to present an abstract of 
the literature on the subject for those unfamiliar with foreign 
languages. 1ST one of the chapters are complete but are intended 
for the use of the general practitioner who wishes an abridged 
discussion of such a subject. While not a believer in the maize 
theory, I have tried to present the matter from the standpoint of 
the zeist as well as the anti-zeist. 

The debt which I must acknowledge to other writers and ob- 
servers is very great. To my teacher, Dr. Joseph Sailer, professor 
of clinical medicine in the University of Pennsylvania, I am 
especially indebted for much help and encouragement. To Sir 
William Osier I wish to express my thanks for help, especially 
in securing certain Italian publications while in Italy as well 
as for the wise advice which he is ever ready to extend to the 
worker in the ranks. To Dr. J. W. Babcock and Dr. C. H. 
Lavinder I am indebted for many kindnesses as well as for their 
splendid translation of Marie's " La Pellagra." The bibliography 
in their work is so thoroughly done that I have deemed a repe- 
tition superfluous and I would refer the reader who wishes it 
to this publication. Much of my work has been done with my 
colleague, Dr. R. H. Bellamy, who with Dr. John B. Wright 
was the first in North Carolina to diagnose pellagra ; this diag- 
nosis was made before the publication of Searcy's work. Many 
of my confreres have rendered great service by according me the 
privilege of studying their instructive and unusual cases of 
pellagra. Among this number I would especially mention the 
name of my lamented friend, the late Dr. W. J. H. Bellamy. 
Among the others are Dr. Thomas M. Green, Dr. John B. 
Cranmer, and Dr. E. S. Bullock of Wilmington, Xorth Carolina. 
To Dr. J. K. Averitt of Cedar Creek, North Carolina, and Dr. 



PREFACE ix 

Dunlop Thompson I wish also to express my appreciation of 
their cooperation. The writings of Casal, Gaetano Strombio, the 
elder, Thiery, Fappolli, Fanzago, Gherardini, Albera, Bona, 
Allioni, Marzari, Hameau, Briere de Boismont, Balardini, Billod, 
Landouzy, Bouchard, Lombroso, Tizzoni, Dejerine, Antoniu, 
Tonnin, Neusser, Baillarger, Tuczek, Belmondo, E. Gaetano 
Strombio, junior, Pellizzi, Marie, Tirelli, Gosio, Babes, Babes 
and Sion, Procopiu, Deiaco, Merk, L., Antonini, Triller, Gregor, 
ISTicolas and Jambon in Europe, to which must be added the 
great work of Professor L. W. Sambon, have been drawn on 
freely. To Professor Sambon I owe my thanks for many kind- 
nesses and great assistance. 

In this country my labors have been greatly lessened by the 
above-mentioned translation with great additions by Lavinder 
and Babcock of Marie's " La Pellagra," by the writings of H. E. 
Harris of Georgia, by the Pellagra Bulletins of the Illinois Board 
of Health, by the work of Dr. George A. Zeller, by the work 
of Dr. J. J. Watson, and by the Pellagra Commission of the 
State of Tennessee. 

Dr. H. A. Cotton, superintendent of the New Jersey Hospital 
for the Insane at Trenton has rendered me great aid with the 
neuro-pathologic work. For photographs I am indebted to Dr. 
J. B. Cranmer, Dr. E. S. Bullock, Dr. J. J. Watson, Dr. J. W. 
Babcock, Dr. C. H. Lavinder, the late Dr. W. J. H. Bellamy, 
the Illinois Board of Health, the Tennessee Board of Health, the 
South Carolina Board of Health, and this does not include many 
others who have aided me by their kindly interest. 

Finally, I wish to express my appreciation of the considerate 
treatment of the publishers who have held up this work for a 
year on account of a serious sickness from which I only recently 
recovered. 

Edwabd Jennek. Wood. 

Wilmington, North Carolina. 



CONTENTS 

CHAP. PAGE 

I. History and Geographical Distribution 1 

II. Theories of Etiology 49 

III. General Characteristics of the Disease 120 

IV. Skin Manifestations 161 

V. The Digestive Disturbances 208 

VI. Nervous and Mental Changes in Pellagra 224 

VII. Diagnosis 286 

VIII. Prognosis 301 

IX. Prophylaxis 312 

X. Treatment 327 

Index 355 



ILLUSTRATIONS 

FIG. PAGE 

1. Casal's idea of the distribution of the skin lesion in pellagra ... 8 

2. Peculiar bodies found in nuclear material from cerebro-spinal 

fluid, in smears from the sensorio-motor cortex, and from a blood 
clot lying in contact with, and posterior to, the lower cervical 

and upper dorsal regions of the spinal cord 98 

3. Professor L. W. Sambon holding a three-year-old pellagrin . . . 101 

4. Map showing pellagra deaths in North Carolina towns 116 

5. Professor Sambon and Umberto Pavinato, aged 3 121 

6. An eleven-year-old negro girl with symmetrical, moist lesions of 

hands, forearms, face, and neck 139 

7. Same patient as represented in Figs. 6 and 8, showing the posterior 

aspect of a Casal collar 140 

8. Same patient as Figs. 6 and 7 141 

9. A row of pellagrous hands 169 

10. Case of Dr. C. H. Lavinder in the U. S. Marine Hospital at Staple- 

ton, N. Y. . . . 170 

11. Skin lesion of the feet 175 

12. Areas of distribution 176 

13. Dr. Zeller's case, showing remarkable distribution and the lamel- 

lated appearance 179 

14. Atypical localization on knees 180 

15. Atypical localization on elbows 181 

16. Atypical and very infrequent localization on the scrotum .... 182 

17. Extensive skin involvement. Author's case 182 

18. Author's case 183 

19. Areas of distribution 183 

20. Areas of distribution 185 

21. Areas of distribution 185 

22. Foot and leg of the patient whose remaining lesions are seen in 

Figs. 23 and 24 187 

23. Dry exfoliating erythematous process on backs of hands .... 188 

24. Photograph of same case represented in Figs. 22 and 23 .... 189 

25. Pellagrous lesions of the hands 191 

26. Deep pigmentation which is more common in Italy than in the 

Southern States 194 



xiv ILLUSTRATIONS 

FIG. PAGE 

27. Extensive areas of involvement of the posterior surfaces of the 

hands, forearms, and arms and a faint Casal collar 197 

28. Boy in the Baptist Orphanage — Tennessee case 203 

29(a). Upper dorsal cord of the seventeen-year-old girl 229 

29(6). Mid-dorsal cord of the seventeen-year-old girl 230 

29(c). Microphotograph of the lower dorsal cord of the seventeen-year- 
old negro girl 231 

29(d). Microphotograph of the dorsal cord of a seventeen-year-old 

girl (negro) 232 

30. Lesion which is not pellagra but occupies same location .... 295 

Charts, 
chart page 

1. Temperature chart of pellagra, author's case 142 

2. Author's case. Combination of tertian and quartan malaria in a 

pellagrin 245 



A TREATISE ON PELLAGRA 

CHAPTER I 

HISTORY AND GEOGRAPHICAL DISTRIBUTION 

The importance of a study of the history of a disease in 
any complete consideration is seldom sufficiently appreciated by 
the student of the present time. This fact has been explained 
on the ground that those capable of writing such history are too 
much occupied with the making of it, and again, the demand 
for such work is so small that there is not sufficient justification 
for the expense and labor involved. To Osier we are indebted 
for a stimulation of this study in this country. He has al- 
ways emphasized the importance of tracing the disease to 
the earliest record whenever possible, just as one would study 
embryology by tracing the ovum through its various stages 
of development to maturity. Both the error of earlier obser- 
vation and also that part which has stood the test of time 
are equally important. In the study of pellagra we are at 
once confronted with a situation which largely hinges on a cor- 
rect history of the disease. Since the earliest descriptions the 
various opinions have been greatly divided regarding the source. 
Many and, in fact, the majority of writers have contended that 
it was a disease of comparatively modern times, never observed 
until early in the eighteenth century. On the other hand there 
are those equally positive in the opinion that it was a disease 
known to the ancients and described by them. This latter school 
considered pellagra a disease which had been mistaken for, or 
confused with, a number of diseases, chief among which were 
leprosy and scurvy. 



2 A TREATISE ON PELLAGRA 

The importance of the history of pellagra is at once appreciated 
when one remembers that the most important contention of the 
zeists * is that pellagra was unknown in Europe until after the 
introduction of maize from North America in the latter part of 
the seventeenth century. Could it be proven that pellagra was 
a disease of some antiquity known in Europe before the intro- 
duction of maize as an article of food, then that food could be 
declared not to be the cause and thereby open the way for a 
fairer consideration of the whole problem of the etiology. Cer- 
tainly, at this time, there can be no problem in medicine, viewed 
from the standpoint of the southern people, of so much impor- 
tance. The reader, then, must overlook the rather lengthy dis- 
cussion of this matter and grant its importance. Certainly, no 
step in the study of pellagra would be half so important as the 
disproval of the corn theory in order to make room for a more 
impartial consideration of the question. 

Much may be said regarding the contention which arose during 
the latter part of the eighteenth century regarding the origin of 
pellagra and its relationship to such diseases as pellarella, pella- 
rina in Pellano, pellarium, purpura chronica, as well as such 
diseases as Mai de la Rosa, and Mai del Padrone, which latter 
names were only synonyms existing, in some instances, before the 
word pellagra was coined by the Italian peasantry. 

Frapolli and Albera considered pellagra an ancient disease, and 
the former thought that there was provision made for it in the 
hospitals since the year 1578. He further stated that some of 
these cases were called pellarella. Albera considered Sennert's 
ephelides nothing more nor less than pellagra in a mild form. 
Strombio, the elder, claimed that there was nothing to the claim 
of Frapolli regarding pellarella except a similarity of name. 
Gherardini believed that pellagra was a modern disease and that 
the name pellarella signified a syphilitic affection. His ground 
for this belief was that the hospital at Broglio where Frapolli 

1 The word zeist is used throughout this work to indicate an advocate of the 
theory that damaged or otherwise diseased maize causes pellagra; likewise the 
term maize will be used always instead of the term Indian corn. 






HISTORY AND GEOGRAPHICAL DISTRIBUTION 3 

reported his cases of pellarella was only for the treatment of 
venereal diseases. While Strombio, the elder, was of the opinion 
that pellagra was a modern disease and that pellarella resembled 
it in name only, he was skeptical regarding this theory of 
Gherardini's. Moriggia x said that the hospital in Broglio called 
Hiob was for the purpose of treating venereal diseases and scabies. 
In Salvator vitale 2 we learn that those suffering with leprosy, 
cancer, and syphilis were brought to the hospital at Broglio and 
we infer from the tone of the writer that cases were also ad- 
mitted with very questionable diagnoses. It would not be un- 
reasonable to suppose that Frapolli had good ground for his belief 
that among these cases were many of pellagra. Certainly it can 
be proven that there were many cases admitted that could not 
be diagnosed as syphilis or venereal disease. It is apparent that 
if this is the only evidence against . the identity of these two 
diseases it must be dismissed. I have been unable after a 
thorough search of the literature to find a single other evidence 
that would tend to prove that these two diseases, pellarella and 
pellagra, were not identical. It seems reasonable to accept 
Frapolli's view of the matter unless better evidence of its incor- 
rectness can be brought forward. It is no unusual thing at this 
time for pellagra to be confused with syphilis, and I know of one 
case at least where the patient was not satisfied with the diagnosis 
of pellagra and went to Hot Springs, Arkansas, for treatment 
and there his condition was accounted specific. If we, in this 
enlightened time, can make this mistake, it does not seem un- 
reasonable that the same thing should have occurred in the six- 
teenth century. 

Strombio differed with Albera, claiming that pellagra was alto- 
gether different from Sennert's ephelides. He said : " The 
ephelides which the Germans call Sommerbrand appears on the 
face, the hands, and other parts exposed to the sun's rays. The 
skin is red in the beginning and then becomes black. The face 
is not so much spotted as it is altogether changed in color, etc. 

1 Moriggia, " Delia Nobilita di Milano." 

2 " Theatrum triumphale Urbis Mediolensis," 1644. 



4 A TREATISE ON PELLAGRA 

How can one compare this with pellagra ? " It would appear ac- 
cording to our present knowledge that such a comparison would 
be very well founded. 

In none of the writings of the ancients was Strombio able to 
find a complete description of pellagra, but he very aptly re- 
marked that it would not be improbable that the old observers 
described it in sections, or rather, that the sum total of these 
various phases would, when united into a whole, make a complete 
description of the disease. It is comparatively an easy matter 
to find in ancient works mention of the various symptoms, but it 
is equally true that none of the earlier writers ever connected 
them into a whole. Strombio wisely remarked in another place 
that Hippocrates speaks of more than one kind of pain which 
" spreads to the neck from the head and from the loins and limbs, 
of fainting, of coloring of the face, tetanus, melancholia, delirium, 
and many other conditions which occur in pellagra." It is notable, 
however, that Hippocrates' description of solliciludo very nearly 
approaches an accurate description of pellagra. He described 
such patients as being slightly delirious in the spring, that they 
avoided the light and companionship of men. and that they seemed 
terror-stricken by the least sound, and had a dread of seeing their 
departed friends and ghosts. The connection between this peculiar 
mental state and the seasonal variation deserves more than a pass- 
ing mention for there is hardly another disease in which the 
spring recurrence is so well emphasized. 

Gherardini thought that pellagra was a modified form of ery- 
sipelas, but Strombio called attention to the fact that this opinion 
was valueless because the observer merely took into consideration 
the skin manifestations without any regard to the systemic symp- 
toms. Strombio made a diligent effort to compare pellagra with 
a number of the diseases described by the ancient writers. He 
said he was impressed by the old idea that pellagra was merely 
a remnant of leprosy. This view seemed to have been founded 
on an opinion of Sauvage's 1 who spoke of lepra asturiensis and 
compared pellagra with different varieties of leprosy. He then 

1 Sauvage, Boissier de' Xosolog. Met. Ord., V, Sp. 4. 



HISTORY AND GEOGRAPHICAL DISTRIBUTION 5 

studied leprosy as it was known to the Greeks, Arabs, and Jews. 
He said, further, that he was impressed by his studies that leprosy 
was a skin disease and that pellagra was a disease in which the 
skin manifestations were only a small part of an underlying 
general condition. He next described elephantiasis, but was unable 
to find any points of similarity with pellagra. Impetigo of Celsus, 
vitiligo, Alphas, Melas, Leuca of the Greeks, Morphaa Alguada of 
the Arabs — in none could he find a symptom common to pellagra. 
He admitted, however, that in many of the descriptions of leprosy 
of the Jews, if considered in the same broad sense as Hippocrates 
wrote, he was able to find symptoms differing little from those 
characteristic of pellagra. In that time leprosy must have been 
a broad term subject to great flexibility and under this term 
were included many different skin diseases which have since been 
separately described. 

It seems remarkable how many writers confused pellagra and 
scurvy. Strombio said that no other disease so closely resembled 
pellagra and pointed out that the filthy and unhygienic manner of 
living of the peasantry predisposed to both. Further he said that 
general exhaustion, diarrhoea, fever, and vagabond pains were com- 
mon to both conditions. He thought that scurvy was favored by 
moist air and dampness, while pellagra usually occurred in the 
hill country. It seems strange that after a century and a half 
Sambon should again emphasize this fact in his effort to work 
out the etiology from the standpoint of the geographical peculiari- 
ties. This observer employs the fact that pellagra occurs more 
commonly in the hill country to prove his contention that the 
disease is transmitted by the intermediate host, the Simulium 
reptans, which lays its eggs only in rapidly running water, hence 
requiring the higher regions. 

In one place Sauvage gave the name lepra scorbutica to the 
disease Mai de la Rosa, but he did not consider it a genuine 
scurvy because in his opinion Mai de la Rosa was an incurable 
disease while scurvy was comparatively trivial. 

Because of the nervous manifestations an effort was made to 
compare pellagra with hypochondriasis, hut in spite of the weak- 



6 A TREATISE ON PELLAGRA 

ness, pains, fainting, melancholia, and even dementia there were 
sufficient distinguishing characteristics manifested to differentiate 
readily the two conditions even in the earlier days. 

Astruc said of pellarella: "It does not differ in many mani- 
festations from our scorbutic pellagra." But he described the 
disease as affecting the palms of the hands and the soles of the 
feet with a pus formation and much furrowing of the skin. 
Strombio thought pellagra might as well be coin] tared with 
syphilis, and he further scoffed at the idea of Videmar that it 
was an old skin lesion on the ground that the natural conditions 
of man were the same and had undergone no change, and further 
that hypochondriasis was an old condition. But Strombio pointed 
out the fact that hypochondriasis was by no means peculiar to 
pellagra. 

Bona thought it was an old disease akin to elephantiasis which 
had undergone great evolutionary change. Videmar mistook a 
disease called solsido by the country people for pellagra, but this 
was probably an error, as it was a very trivial condition, thereby 
differing from pellagra. Allioni took Strombio to task for con- 
cluding so positively that there was no connection between his 
purpura chronica and pellagra. 

It is likely that our present idea of the modernity of pellagra 
owes its origin largely to the writings of the above oft-mentioned 
Gaetno Strombio. It is only right that the work of this man 
should be given most respectful attention, for he wrought valiantly 
in his day and time. His writings show great accuracy and a 
wonderful power of observation, entitling them to favorable com- 
ment as accurate scientific work, even by the fierce light of 
modern criticism. Probably no man before or since his time 
was given such opportunities for the study of the disease. In 
1784 the first hospital for the treatment of pellagra was estab- 
lished under a grant of Joseph II of Austria, and Strombio was 
placed in charge of it. At the close of 1788 this hospital was 
abandoned and Strombio was given charge of the greater hospital 
of the same character in Milan. This position was held for three 
years, and during that time his observations were made. He 



HISTORY AND GEOGRAPHICAL DISTRIBUTION 7 

mentioned the fact that his observations were on a sufficiently 
large number of cases to entitle him to arrive at logical con- 
clusions. It is important to weigh Strombio's conclusions with 
great care. We naturally conclude that he was prejudiced and 
could see the matter from the one standpoint, — that of a modern 
disease. On the other hand we should consider that in the more 
recent history of pellagra it is a notable fact that wherever it 
makes its first appearance there it is, for a time at least, con- 
sidered a new disease, and many fantastic names have been coined 
to designate it, as psilosis pigmentosa * in Barbadoes. Even in 
the United States many physicians refused to acknowledge that 
the disease appearing in almost epidemic form in certain sections 
about the year 1905 was pellagra. I count myself among the 
number of those who refused to consider this disease under its 
proper name for a long time after its first appearance. We note 
the statement of Strombio that in the pellagra contest of the 
jSTational Society of Milan the thesis of Videmar was not pub- 
lished. This thesis was entitled " ISTil novum sub sole." Like 
this writer, there have been observers in every generation who 
would not accept the idea that pellagra was a new disease. From 
what has been said above one would infer that there is good 
ground for the idea that pellagra was an old disease which could 
readily have been confused with a number of other diseases or 
conditions, and further, that if in this enlightened time when 
medical literature has added so much to the physician's arma- 
mentarium there is still so often doubt of the diagnosis, it would 
be only fair to presume the occurrence of error in the earlier 
times. 

In 1735 a physician of Oviedo, Gaspar Casal, who is desig- 
nated as protomedicin de Castille by Roussel and also as physician 
to Philip V, described a condition among the poor inhabitants of 
the country which he called " a kind of leprosy, very singular.'' 
This first observation was made on eight cases under date of 
March 26. He never used the term pellagra, which was coined 
probably years later, but always Mai de la Rosa, though I have 

1 Trans. Pan-American Medical Congress, 1893. 



8 



A TREATISE ON PELLAGRA 



never found evidence that he considered this name to have been 
coined by him. The Italian and French physicians did not accept 
the idea until 1845 that the disease described by Casal was the 
same as that described by Frapolli and called by him pellagra. 

This latter observation was 
made in Lombardy thirty-six 
years later. The idea of the 
identity of pellagra and Mai de 
la Rosa was never seriously con- 
tested according to Eoussel, who 
stated that his idea of the unity 
of the two diseases was borne 
<mt by the unanimous assent of 
the Spanish physicians in 1847 
and likewise by the Academy of 
Medicine in 3849. 

The Academy of Sciences in 
August, 1847, formulated the 
query, " Spanish pellagra called 
Mai de la Rosa, is it not a form 
of pellagra ? " 

The volume in which are 
found Casal's records was writ- 
ten in Spanish, but the medical 
portion is in Latin. 1 Roussel 
said that this work was so little 
known out of Spain that in 1843 he was the first to consider the 
question of the identity of Casal's Mai de la Rosa with Italian 




deiiqruxnt. 
KCCjfCetacao-pvxjLijm, 



Fig. 1. — Casal's Idea of the Distri- 
bution of the Skin Lesion in Pel- 
lagra. 



1 " Pree vernaculis aliis affectionibus dominatrix merito regionis hujus scabies 
appellari debet. . . . Secundus, a scabie. endemicus morbus est lepra. . . . His 
adhibere possvnnus malignum quamdam lepra? speciem, qua? singularissima est, 
et hie patrio voeabulo, Mai de la Rose, nuncupatur. . . . Cum videssem uullam 
vernacularum affectionum horribiliorem. eontumaeioremque, non abs re fore 
putavi me historiam seribere." — " Historia natural y medica de el Prineipado 
de Asturias," Abra posthuma del Doctor D. G. Casal. Medico de Su Magestad y 
su Protomedicin de Castilla. Madrid. 1762. Edited by Juan Garcia Sevillano. 
There recently appeared a new edition of Casal's work. The medical portion, 
which was originally written in Latin, in this edition is in Spanish. 



HISTORY AND GEOGRAPHICAL DISTRIBUTION 9 

pellagra. This claim was substantiated by Thounel, Strombio, 
Cerri, and Marzari, but none of these observers so well appre- 
ciated this fact as did Royer in 1834. 

Roussel 1 made his report to the Academy of Medicine in 1849, 
giving the result of a voyage of medical inspection of seven 
months' duration. He made twenty-two observations in the same 
territory in which Casal's work was done and stated even more 
positively than formerly the correctness of his original opinion. 
He stated that there could no longer be any doubt on the question 
of the identity of pellagra and Mai de la Rosa and explained 
the late recognition of this fact on the ground, mentioned above, 
that Casal's work was so little known out of the territory in 
which his observations were made. This is illustrated in the 
writings of Thiery, 2 published in 1755 in the Journal de 
Vandermonde. This writer was at that time a regent of the 
Faculty of Paris and had been an ambassador of Louis XV in 
Madrid and at that time had known Casal at the court of Philip V. 
He made careful notes of his recollections of these interviews and 
also of his. reading of Casal's manuscripts, and this record forms 
a valuable chapter in the history of the disease because it helps 
to fix the date of Casal's writings, which has been disputed by 
some who have claimed that he did not make his observations as 
soon as 1735. Thiery's " Notice " became celebrated. It was 
an abstract of an address delivered to Chomel, dean of the Faculty 
of Paris. In his writings he called the attention of the medical 
world to pellagrous erythema observed, according to him, in the 
Asturias. At this same time the disease was described in Italy 
by Pujati and Jacopo Odoardi 3 in the Venetian states, where it 
was known as Alpine scurvy. In the same year Lombardy was 
ravaged by pellagra. Soon after this Sauvage in his outline of 

1 Roussel, " Eapport transmis a l'Academie de Medicine, par M. le ministre 
de l'agriculture, du commerce et des travaux publics, le 27 fevrier, 1849." Bul- 
letin de l'Academie, t. XIV, p. 572. 

2 Thiery, ." Rec. period, de med. et de chir." Paris, 1755, t. II, p. 337. 

3 " Contribution a l'etude de la Pellagre et du Syndrome pellagreux," par 
MM. J. Nicolas et A. Jambon. (Clinique des Maladies cutanees et veneriennes 
de PAntiquaille de Lyon.) Annales de Dermatologle et de Syphilographie, 1908. 
4. Serie, p. 385. 



10 A TREATISE ON PELLAGRA 

" Nosologie methodique " attempted to place Mai de la Rosa 
under the name lepra asturiensis as the fourth species in the 
genus lepra in the group of cachexias. 

Thirty years after this an Englishman, Dr. Townsend, traveling 
in Casal's territory, made some observations on pellagra which 
he had noted. He visited the hospital at Oviedo and was given 
all the information available by the physicians, Antonio Durand 
and Francisco Nova. This information, according to Roussel, 
was of little importance. This latter writer made a thorough 
search of Spanish literature in an effort to determine if the 
disease described by Casal and later mentioned by Townsend had 
disappeared from Spain. He was able to discover only that Un- 
celebrated writer, Feijoo, in a letter written to Casal under date 
of December 2, 1740, announced that Mai de la Rosa existed in 
Galicia, his native country. He further wrote that Dr. Batalla 
of Santiago in 1859 had said that sufficient importance had not 
been accorded to the opinion expressed in a work entitled " Teatro 
Critico." I have not been able to secure a reading of this work, 
but presume from Roussel's writing that this was another account 
of pellagra in Spain which had never attracted any attention. 
According to Roussel's research there were no writings in Spanish 
from the time of Casal's account to the year 1826, when an 
article appeared in the Barcelona Journal de Medicine, which 
mentioned the existence of pellagra in the environs of Alcaniz 
in Aragon. Either pellagra did not exist in Spain during this 
period or else it was omitted in all medical writings. In 1846 
Roussel appealed to Professor Orflla, who made inquiry of one 
Dr. Gonzales Crespo of Guadalajara, who in turn stated that 
nothing had been published on the subject since the posthumous 
work of Casal in 1762, and further, that the existence of Mai 
de la Rosa had not been noted out of the Asturias. 

Dr. Gimeno wrote to Hi jar of the district of Alcaniz under 
date of October 22, 1826, the following letter, which was pub- 
lished in the Diario General de las Ciencias Medicas at Barcelona: 

" Since I have finished my studies and established myself in this 
country to practice medicine I was surprised regarding this 



HISTORY AND GEOGRAPHICAL DISTRIBUTION 11 

affection which I wish to describe. The cause of the chronicity, 
of the complexity of the symptoms, and still more of the incura- 
bility made me consult the few books that I had and the old 
physicians of the neighborhood ; I did not find any light. Only 
in the dictionary of Boliano, under the name Mai de la Rosa 
of the fourth species of the genus lepra, was I able to find any 
reference. I find something analogous with regard to the inter- 
mittance and of the same type; but in the remaining symptoms 
they differed sufficiently to distinguish them. Above all I was 
not satisfied with the plan of treatment. 

" In October, 1820, I addressed a circular to six physicians 
of the neighborhood. Of those who replied to me their descrip- 
tions conformed to my own. . . . The disease described under the 
name pellagra resembles more or less and is analogous to that 
which I have mentioned in the history sent you. This history 
was the result of only one hundred observations in the space of 
eleven years. With regard to the nature of the disease I am of 
the opinion of the other writers that it is a chronic gastroenteritis 
added to a disturbance of the hepatic system. The liver was found 
in a state of phlegmasia, but a phlegmasia sui generis, distinct 
from the others." 

The descriptive document annexed to the letter of Dr. 
Gimeno bore the title " Histoire ou description de la maladie 
vulgairement appelee Mai del Higado." This latter name 
indicated a disease of the liver. The author described a 
disease which was common to a large number of inhabitants of 
the villages (pueblos) of the district of Alcaniz and of some 
of those of Daroca, Terruel, and Morella. He claimed that it 
was hereditary but not contagious. " It could not be considered 
endemic," said Gimeno, " on account of the diversity of the 
situation, of the temperature, of the soil, and of the locations 
where it occurred." 

In 1847 Mendez-Alvaro 1 wrote that in November, 1835, he 

1 Mendez-Alvaro, Boletin de medicina no chi, 2 Septembre, 1847. " Noticia 
sobre la pelagra el doc. D. F. Mendez-Alvaro." 



12 A TREATISE ON PELLAGRA 

noted in Villamajor de Santiago, a province of Guenca, a num- 
ber of people who had a skin lesion on the backs of the hands 
and anterior surfaces of the forearms which was characterized 
by small scales producing a cooked appearance of the inflamed 
skin. The skin was thickened and itched slightly. The first 
patients were females who were very poor. These people used 
a form of lye which was a substitute for soap. It was thought 
that this caused the disease, but the writer soon disproved this 
theory by finding the disease in men as well as in women. He 
further noted that these patients were often delirious and the 
disease was followed by a sort of dementia which they called 
flema salada. In the months of January and February, 183(5, 
he saw several patients with vertigo and cerebral symptoms which 
were thought to be secondary to the skin affection. One of the 
patients died and a large number had cutaneous desquamation, 
especially on the arms and hands. The description of Mai dc la 
Rosa by Casal did not give a complete picture of the condition, but 
the writer was impressed by the analogy, especially when he took 
into consideration the nervous and gastrointestinal symptoms. It 
was finally decided that the two conditions were one and the same. 
This report of Mendez-Alvaro is the first record of the disease 
flema salada, which must have been pellagra, though the eighteen 
years of its observation left no very accurate account of it. and 
after this period had elapsed the disease seems to have disappeared, 
due, in all probability, to the better knowledge of pellagra whereby 
the diseases were shown to be identical. There were three 
Asturian physicians to follow up this work of Mendez-Alvara. 
One of these was a physician of the province of Leon, Juan Andrez 
Enriques of Fermoselle, who described the occurrence of flema 
salada between the Duoro and Tormes rivers. He was unable 
to find any record of a similar condition in any of the medical 
authors of that day, though he found several symptoms that 
suggested Mai de la Eosa. This writer dismissed the matter 
without any great amount of study, hoping that time would clear 
up the mystery, though he resented bitterly the coming of 
foreigners to help out the sufficiently wise Spanish physicians. 



HISTORY AND GEOGRAPHICAL DISTRIBUTION 13 

At the same time this observer spoke of Mai del Monte, 
which in all probability was pellagra. It affected both sexes 
alike and occurred only in the poor. It was supposed to be 
hereditary and was always chronic. Its duration was indefinite 
and it often lasted throughout life, the patient in some cases 
reaching a great age. He described it as affecting the skin of 
the backs of the hands up to the middle of the forearm. The 
skin became almost transparent, shiny, and parchment-like. The 
patients had vertigo, illusions, and often an intermittent dementia. 
The country people spoke of it as Mai del Monte or Mai el Monte. 
In the section where this condition was found were a number 
of unfortunates who, though previously healthy, became ema- 
ciated and depressed. The face became sad and the expres- 
sion fixed. The words were always enunciated very slowly. 
The patients were usually emotional. At times there were skin 
disturbances, which suggested burns and for which the disease 
was often mistaken. It is interesting to note that this same 
mistake has been made in this country in recent years before the 
existence of pellagra had been recognized, and many attendants 
in institutions have unjustly lost their positions on account of 
the authorities supposing that the skin lesion of pellagra was a 
burn caused by carelessness in giving too hot a bath. This con- 
dition was further described as causing a slow movement of the 
limbs, a mental action which was retarded, suggesting that the 
mind was laboring heavily when considering the simplest things, 
and an unwillingness to take food necessitating the actual placing 
of food in the mouth. There was no taste and no desire for food. 
The sphincters finally became relaxed and the patient died in 
a condition of dementia. It was an accepted idea that the disease 
was incurable. The writer concluded his report thus : " I beg 
the physicians of the Asturias and other places where this disease 
occurs to publish the histories of their cases in order to determine 
if the disease is the same and to find out some curative measure 
which will give better results in rescuing these poor victims from 
a deplorable death." 

Insufficient as was this publication, Roussel remarked that 



14 A TREATISE ON PELLAGRA 

Enriquez by it made known the fact of the existence of a pella- 
grous or pellagroid epidemic in the province of Zamora near the 
frontier of the Portugese province of Tras os Monte. 

Of the Asturian physicians who responded to the appeal of 
the Madrid journal, Iligino del Campo took first prize. In an 
article in the Boletin de Medicina for October 10, 1S47, under 
the title of " The Value of Sea Water," he extolled sea water 
in the treatment of Mai de la Rosa. The Spaniards found much 
fault with the writings of Del Campo, but in spite of the unjust 
criticism of Casal and in spite of the faulty idea that in the blood 
of the pellagrin there was an accumulation of heat, his work was 
valuable because it showed the disease as it was found in the 
Asturias and indicated careful study and observation. 

Del Campo thought that there was a difference between the 
so-called Color del Higado and the disease described by Casal. 
He said: " I have never observed those traces of rough and shining 
cicatrices which Casal considered pathognomonic." A great deal 
of heated comment among the Spaniards was caused by this 
criticism of their idol, Casal. Roussel well said that Del Campo 
seemed to disregard the stage of the skin lesion, as it is a well 
recognized fact that at the various stages of the skin manifestation 
there is a decided difference in the character and general appear- 
ance. Antonio del Valle objected to this criticism of Del Campo 
because there was no mention by this latter observer that at one 
stage the skin areas affected were dark red without exfoliation, 
that the appearance was of a shining brilliance resembling the 
marks made by burns. He was confident that Mai de la Rosa 
and Color del Higado were a single disease. After a pompous 
eulogy of Casal he spoke of the frequency of the disease, claim- 
ino- that there was in the Asturias one such case to everv six 
hundred inhabitants, but it was otherwise estimated that there 
was one to every three or four hundred. 

Valle said that the disease was a chronic affection of an ex- 
anthematous form, though often squamous, of a dark rose color; 
that it occurred by predilection on the parts exposed to the sun's 
rays, especially on the metacarpal and metatarsal portions, though 



HISTORY AND GEOGRAPHICAL DISTRIBUTION 15 

sometimes on the lateral portions of the neck and the superior 
and anterior parts of the chest. It developed with all its in- 
tensity in spring with the coming of hot weather. It was con- 
stantly preceded and accompanied by profound functional dis- 
turbances. The cerebral manifestations, according to him, were 
more than the digestive. The symptoms, especially of the skin, 
decreased with the approach of winter. The skin where occurred 
the erythema was described as having a dull rose red color without 
any desquamation, appearing much like the traces left by a burn, 
The chief nervous disturbances were given as slight vertigo and 
other trivial nervous affections which, when they became severe, 
presented conditions most difficult to treat. He said : " If this 
affection is called pellagra, there can be no doubt that in those 
old principalities, where a condition from time immemorial has 
been called Mai de la Rosa and Mai del Higado, is true pellagra, 
inasmuch as it embraces all these conditions." He further said 
that if the word pellagra, according to its Italian meaning, sig- 
nified fissures or erosions of the skin, it agreed with Mai de la- 
Rosa or Asturian pellagra, for it occurred in the same manner 
as had been described by Cjasal, who was spoken of as the " Hip- 
pocrates of the Asturias." Profundis scepissime inter cisam fts- 
suris ad vivam asque carnem penetrantibus. 

Roussel analyzed the writings of several Spanish physicians 
under the title " La Pellagra y Mai de la Rosa," and made the 
following synopsis : 

(1) That pellagra up to the year 1847 had received no careful 
study in Spain ; that no part of it had received careful observation 
sufficient to furnish a reliable description or consideration of the 
etiology. 

(2) That beyond the endemic pellagra of the Asturias there 
existed other identical endemics which so nearly resembled it that 
in the state of the knowledge of the disease it was very difficult 
to designate them under other names. 

(3) That the endemic pellagroid or pellagrous districts were 
found in a large number of places far distant from each other. 
The disease occurred in the north and also in the central part of 



16 A TREATISE ON PELLAGRA 

Spain. From 1820 to 1826 one of these outbreaks went by the 
name Mai del Higado and occurred in Aragon, in many places in 
the province of Terruel, in the river valley of the Ebre, in the 
basin of the Gaudeloupe, and in the environs of Alcaniz and 
on the borders of Xiloca in the environs of Daroca. In 1835 
there was recognized a strange malady under the name flona 
salada in the upper basin of the Guadiana, in the province of 
Guenca, in New Castile, and possibly in other places. In 1847 
an endemic occurred under the name Mai del Monte or Mai el 
Monte near the frontier of Portugal, in the basin of the 
Dauro, and in the province of Zamora. There also occurred 
Mai de la Rosa in the Asturias where Casal first found it. It 
extended from the coast between Aviles and Gijon to the foot of 
the mountains. 

(4) It is granted that all these endemics, however imperfectly 
studied, have the appearance of Pellagra, which in Spain, accord- 
ing to geographical, topographical, and climatic reports, together 
with certain points of variation, presents a general similarity of 
such a nature that the unity of the disease cannot be doubted. 
In all cases it was found to occur in country people and in workers 
in the earth, and especially in the very poor. 

In 1859 Batalla called attention in the Siglio Medico to the 
fact of the reported observation of Feijoo, which was made in 
1740. He also showed the correctness of this report which re- 
lated the presence of Mai de la Rosa in Galicia. This observation 
was based on sixty-four cases, but the object of the paper seemed 
more for extolling the virtue of sulphur baths in the treatment. 
Batalla found the disease essentially in middle life and more 
common in men than in women, and he further noted the im- 
portant fact that all of his cases were from the country districts 
and were poor people. The disease was attributed to poor maize. 
In the clinical description there was no difference from that of 
the Italians of the same period. His idea of the etiology caused 
disagreement among his confreres. This opposition came from 
the mountainous regions of Castile and Aragon where Mendez- 
Alvaro had observed it under the name flema salada in 1835. 



HISTORY AND GEOGRAPHICAL DISTRIBUTION 17 

This latter condition was spoken of as Mai de la Rosa, with some 
slight variations which had resulted from climate and other 
circumstances. In the journal Siglio Medico were published 
from Perrote de Villahoz, Marti, de Villarejo, de Salvanes, and 
Calmarza announcements that pellagra under the name flema 
salada was endemic in their practices and among those who did 
not use maize. Roussel, to whom I am indebted for practically 
all this information regarding the history of these various en- 
demics under many names, but always of true pellagra, takes 
Eatalla to task for what he called his many contradictions. This 
was evidently due to the one fact that Batalla had the courage 
to describe pellagra in those patients who had never eaten maize. 
Had all the observers had the courage of this man the etiology 
would have had much better chance of being settled. 

Costallat denied the identity of the two endemics, but Roussel 
thought that he did not establish his position by good descriptions 
of the condition nor on any evidence of detailed observation. Be- 
cause of this objection which had arisen in Spain Costallat went 
through the Pyrenees and arrived in June, 1860, at Villahoz and 
Mahamud. This excursion of medical investigation was described 
in two articles. One of these was a letter to Landouzy which he 
entitled " Pellagra and Acrodynia," and this was followed by an 
article in Spanish under the title " The Disease Known in Spain 
under the Name Flema Salada Is ISTot Pellagra," which bore the 
date of 1861. He considered the disease merely as acrodynia 
in an endemic condition. He summed up the differential diag- 
nosis in the ten following points : 

(1) The erythema is more pronounced but more definitely cir- 
cumscribed on the hands and feet. A patient was mentioned who 
had been sick for eighteen months and had the erythema in the 
space between the first and second metacarpal bones. The lesion 
had acquired the character of a superficial ulcer surrounded by 
scales and thick scabs. Costallat observed that nothing of this 
kind was ever observed in pellagra. 

(2) A peculiar sensation in the plantar surface of the feet 
when the patient walked, which is compared to walking on cobble 



18 A TREATISE ON PELLAGRA 

stones. This phenomenon Costallat said that he mentioned re- 
garding the epidemic of Paris (acrodynia). 

(3) A dark color of the skin of the wrists, the feet, the arms, 
the thighs, and also of the body was mentioned and described as 
a chocolate color. The writer never saw anything like it in 
pellagra. 

(4) None of the patients had the characteristically furrowed 
tongue of pellagra. 

(5) From Perrote Costallat learned of a sign to which he 
seemed to attach considerable importance : a swelling of the con- 
junctivae with lacrimation. 

(6) lie thought that formication was more a symptom of 
acrodynia than of pellagra, and mentioned its occurrence in this 
series of cases and said that the trouble was confined to the hands 
and feet. 

(7) Paraplegia was counted a differential point of moment. 
It was claimed to be more often present in flema salada than in 
pellagra. It affected more commonly the lower extremities and 
was an indication for a grave prognosis. 

(8) Costallat found the age of the patient an argument for his 
diagnosis. His youngest affected with pellagra was five years, 
while Perrote's youngest was forty-four. 

(9) Perrote never saw in acrodynia suicide nor even a ten- 
dency to it, Costallat refers to suicides in pellagra occurring 
especially in Lombardy. 

(10) Acrodynia is much more rapid in its course than 
pellagra. 

Roussel concluded that the question of the identity of flema 
salada was the most obscure and interesting point in the history 
of pellagra in Spain. The question at that time seemed to have 
been how could pellagra occur without the eating of maize. Had 
the victims of flema salada presented the history of maize con- 
sumption it is hardly probable that this difficulty would have 
arisen. It is a notable fact that in recent years when nearly 
every writer has espoused the maize theory of Lombroso little 
or no mention has been made of this condition which caused so 



HISTORY AND GEOGRAPHICAL DISTRIBUTION 19 

much contention in the time of Costallat. This latter writer 
thought that errors in cultivation, especially an absence of lime 
in the soil, rendered the cereal subject to alterations, and as a 
result there occurred a disease which seemed to be acrodynia or 
what he called " cereal convulsion " occurring in epidemic form. 

It is altogether probable that acrodynia has in some instances 
been confused with pellagra in this country, and I have in mind a 
case described to me by one of my confreres who thought it was 
a case of pellagra. It is no less a difficult differential diagnosis 
at this present time. 

As before stated, Gaetano Strombio was the first of the Italians 
to describe pellagra, and probably no work since that time has 
added materially to the account which he gave. 

Sixteen years after the description of Casal the " Notice " of 
Thiery was published under the name Mai de la Rosa. Simul- 
taneously in many parts of Italy there appeared reports of the 
same condition. A physician of the Hospital Majeur of Milan, 
Francisco Frapolli, in 1771 published an important work entitled 
" Animadversiones in morbum vulgo pelagram." Four years after 
this a physician of Oannobia, Francisco Zanetti, mentioned the 
appearance of the disease on the shores of the Lago Maggiori and 
refers to it thus : " Nemo quern ipse sciam usque a dime de haec 
cutis affection e peculiar iter scripsit." He said that the disease 
was vulgarly called pellagra and affected chiefly the poor and mal- 
nourished. In 1776 a physician of Bellune, Jacopo Odoardi, 
wrote of a form of scurvy which he designated scorbuto alpino. 
Antonio Pujati, a professor in the university at Padua, described 
the disease under the names pellarina, scottura di sole, colore del 
fegato, mal della spienza. He considered it a special kind of 
scurvy occurring in the sub-alpine region. 

In 1780 Michel Gherardini, a physician of the Hospital Majeur 
of Milan as Frapolli had been, wrote an account which was the 
best that had appeared up to that date. About this same time 
Albera's work appeared, as has been mentioned on a previous 
page. At the time it caused considerable comment and has left 
the name indelibly connected with the early history of the disease. 



20 A TREATISE ON PELLAGRA 

Roussel referred to this work of Albera's as being mystico-scien- 
tifique. Albera spoke of a disease caused by insolation, which 
he said was vulgarly called pellagra. 

In 1791 Sartago described scorbuto montano, occurring in the 
territory of Aviano. It was found to conform to the general 
description of Strombio. At about this same time Allioni first 
recognized the malady in Piedmont. 

In 1810 Marzari published his work entitled " Essai Medico- 
politique," in which he said that he had recognized pellagra in 
practically all the new provinces which Napoleon had created 
beyond the Alps. It was this same Marzari who first gave impetus 
to the maize theory of the etiology, although this view had been 
advocated by Strombio and others of the same period many years 
before. He laid particular stress on the fact that polenta was 
consumed in great quantities by the Italian peasantry and that 
they ate no meat or other kind of food. He was of the opinion 
that maize was one of the chief causes, but we note that he does 
not look on it as a specific ; it appears that he merely counted it 
as one of the evidences of poor hygienic conditions. This same 
writer discussed at considerable length the chemistry of maize. 
His experience was drawn from twenty years' study of the disease 
as he found it in the country of Trevisan. Roussel consid- 
ered the work of this man to have been of inestimable value 
because of his clear advocacy of the damaged maize theory of the 
etiology. 

From this time the history of pellagra in Italy is the history 
of the development of the maize theory. It is to be regretted 
that some of this energy could not have been directed to the study 
of the clinical manifestations of the disease. Though the Italians 
had all the clinical material needed, practically no progress was 
made along this line after the work of the elder Strombio whose 
writing has been mentioned frequently. 

Roussel is author of the statement that Professor Franzago 
inserted in his " Memoire," published in 1815, a reclamation 
of his previous opinion regarding the etiology and his acceptance 
of the maize theory. He said: 



HISTORY AND GEOGRAPHICAL DISTRIBUTION 21 

" I take this occasion to inform my readers of the opinion of 
a recent writer on this question. Doctor Gfuerreschi in his 
' Observations sur la pellagra/ published in the Journal of Parma, 
is certain that melica (a name signifying maize) is the true and 
only cause of pellagra and he expressed the hope that henceforth 
pellagra be called Raphania maistica. He noted that the numer- 
ous and varied causes given in the past were not sufficient to pro- 
duce the disease. He then spoke of the bread called milange, 
which in the past had been in general use. It was composed of 
wheat flour, of beans, of German wheat or spelt, of rye, and added 
that at the time of his writing maize and maize alone had taken 
the place of this compound food entirely. Wheat had become a 
rare plant. . . . He said that all the pellagrins whom he had 
examined replied in the affirmative when asked if they ate polenta 
and further declared that it was their only food." 

About twelve years before this time Thouvenel had called 
attention to a new malady which he thought at that time might 
be readily eradicated. Marzari said that the only way to rid 
Italy from the ravages of pellagra was to supply the poor with 
bread made of wheat, meat, and potatoes, but to teach the peasantry 
the importance of such a change in their manner of living he was 
unable to do. 

In 1787 a young Frenchman, Lavacher de la Feutrie, followed 
Jansen and Hollen-Hagen in the study of pellagra. He studied 
the disease in Lombardy, and about the year 1802 communicated 
to the Societe Medicale d'Emulation the results. In 1806 it 
was made a special publication. There was no further reference 
in the French medical literature until 1829 when Briere de 
Boismont made his observation, although there was abundant op- 
portunity for the study of the disease. There was, however, one 
case of a French soldier observed by Husson in the Hotel Dieu 
and later by Alibert in the Hospital Saint Louis. This case did 
not attract as much attention as its importance deserved. Biett, 
who had observed pellagra in Italy, did not make the careful 
study at this time that did Alibert, who classified it as a dermatosis. 



22 A TREATISE ON PELLAGRA 

Two articles of merit were published at this time in France. 
One was " L' Article Pellagra," published in 1819 by Jourdan 
in the Dictionnaire des Sciences Medicates. The other was a re- 
port on Mai del Higado by Dr. Gimeno in 1826. He identified 
this condition, which was found in Alcaniz to be the same as the 
pellagra of Italy. Still another important work was published 
in 1831 by Kayer. 

The work of Briere de Boismont was published in 1830 after 
its presentation to the Academy of Science and was of the greatest 
importance, because it called attention to the fact that within a 
few miles of Paris the disease occurred in the thousands, and he 
complained that there had not been enough attention paid to the 
matter by the medical profession. There were others to add their 
testimony to the correctness of his claim regarding the prevalence 
throughout France. At this same time the malady appeared un- 
recognized in the southwest portion of Italy. It had already been 
noted in 1829 that the disease was attacking the poorer classes 
in the lower parts of Arcachon, and the fact of the identity of this 
disease with Italian pellagra had been already mentioned by sev- 
eral physicians in Bordeaux. In spite of this report the medical 
profession of this section had not been interested and even the 
physicians of Paris, among which number was Briere de Boismont, 
had not paid the matter the slightest attention. There were a few, 
however, who did study the disease at this period in the face of 
this general apathy of the profession, and they deserve particular 
reference. Among "this number the most important contributor 
was Hameau, 1 whose writings have always been counted of the 
greatest importance. 

In 1818 this physician of Teste de Buch, Dr. Hameau, had 
under his care a woman whom the physicians considered was 
suffering from an obstruction of the bowels. The patient was 
markedly malnourished. She had three daughters in good health. 

1 Hameau, J. M. G., " Une maladie peu connue observee (en. ISIS) dans les 
environs de la Teste." Soc. Royale de Med. de Bordeaux, 1S29. Jour, de Med. 
de Bordeaux, 1829, Bull, de I'Acad. de Med., 1832. — " Description d'une mala- 
die nouvelle observee sur le littoral du bassin d'Aracbon." Bull. Acad, de Med., 
Paris, 1837-1838. — "De la Pellagra," 1S53. 



HISTORY AND GEOGRAPHICAL DISTRIBUTION 23 

In 1819 he was called to the same house to see the youngest 
daughter, who was affected similarly to the mother. Soon after 
this patient appeared cured. In June, 1820, however, she returned 
to Hameau and reported that for one month she had suffered a 
return of the former symptoms. In 1821 he was called the third 
time to attend this same patient, whom he found in a serious 
state. She died in February, 1824. In his work in this neigh- 
borhood Hameau was constantly reminded of this case by numer- 
ous repetitions of the same symptom complex. He was of the 
opinion that the same condition existed over a much larger terri- 
tory than the field of his observation, and he was impressed with 
the gravity of it. In 1824 (May) he acquired a new case from 
a farming community and he noted what he considered a re- 
markable condition, two cases in one family. His records show 
numerous cases and his description indicates the carefulness of 
his observation. In 1829, before the Royal Society of Bordeaux, 
he presented a report on " a disease little known which was 
occurring in the environs of Teste." He described it as a disease 
of the skin about which the literature had little to say. This 
disease was menacing the country from which he came and he 
wished to mention the chief symptoms in the hope that he would 
be able to secure some aid in giving relief to the unfortunate 
victims. This writing was published in the Journal de Medecine 
Pratique of Bordeaux, and the Society of Medicine invited a 
conference of the physicians interested to consider the matter. 
The secretary, Dupuch-Lapointe, reported that Hameau presented 
many of the phenomena which the Italians had described as 
occurring in pellagra and it was the opinion that there was an 
analogy between the two conditions. Gintrac and Bonnet went 
a step further and declared the two conditions identical. All the 
facts in the case were developed in Hameau's second work, the 
" Memoire," which, while an important work, attracted only local 
attention. Following this the disease was recognized in the dis- 
trict of Brazas. A young physician of the Teste, Lalesque, studied 
it further and wrote a monograph, which he addressed to the 
Council of Health of Bordeaux. Soon after this the physicians 



24 A TREATISE ON PELLAGRA 

of the Landes, Ardusset and Beyris, proved the identity of this 
condition and Lombardian pellagra. From this time the term 
maladie de la Teste was supplanted by the better term pellagra 
des Landes. 

The extent of the disease as well as the gravity soon alarmed 
the authorities of the Gironde and they selected Leon Marchand, 
the physician in charge of infectious diseases, to make a new and 
more complete study. This action was confirmed by the Minister 
of Agriculture and Commerce in 1830. Many years were de- 
voted to this work, and in 1843 he wrote a monograph for the 
Paris Academy of Medicine in which the number of cases avhs 
estimated at one hundred in the district of Linx. He found that 
Hameau had made his observations on seventy-six cases and 
further that these patients were country people, especially workers 
in the earth and shepherds. Xot only did he find it in the poor, 
but also in better conditioned people. He found, however, that 
the victim was always poorly nourished. From 1830 to 1842 
Marchand found pellagra in all of the twenty communes of the 
Gironde. It was noted at this time that it was a disease not 
occurring in the cities. There was only very rarely a case 
in Bordeaux. Roussel mentioned that in the hospital Saint 
Andre with seven hundred patients there was only one case of 
pellagra. It was found that in at least one instance the disease 
was confused with Pompholix diutinus. 

When Billod 1 made his observation on the disease which was 
known as pseudo-pellagra, the first tangible objection to the maize 
theory was formulated, for the only difference between pseudo- 
pellagra and pellagra was that in the former no maize was eaten, 
while the reverse was true of the latter. The question was asked: 
" Is this variety of pellagra described by Billod in the insane 
to be considered as pellagra ? " Roussel thought not and gave as 
his reasons that the disease occurred in people who had not eaten 
corn and in sections where it was not known. It would have been 
more scientific if this distinguished pellagrologer had reasoned 

1 Rapport de 1'epedemie de Sainte-Gemmes avec la pseudo-pellagra de Billod 
et de Beri-beri. Paris Thesis, 1899, by J. Martin. 



HISTORY AND GEOGRAPHICAL DISTRIBUTION 25 

forward instead of backward. It is likely that much of the subse- 
quent confusion would have been avoided and while the question 
might have remained unsolved, the true solution would have been 
much more likely. I have studied the case reports of Billod 
carefully and am convinced that if this disease was not pellagra, 
then pellagra does not occur in the United States and we have 
fallen into a great error. Billod's description is exactly the same 
as the description of the disease known as pellagra in the southern 
states and is the same pellagra which Babcock and Williams 
observed in Italy recently and found to be the same as the disease 
in South Carolina. 

Gintrac wrote, according to Roussel, the following : " The maize 
which is collected in the Landes de Gascogne is carried to Teste 
where it is consumed ; it is frequently damaged. Hameau found 
in the granaries a large quantity of verderame, but in spite of 
this fact not a single case of pellagra has been observed in Teste." 
On the other hand Costallat said that he had never observed a 
case in which a definite history of maize consumption was not 
obtainable. 

Lemaire, the health officer of Minizan, who had observed the 
disease for many years, regarded it as peculiar to the section 
and affecting country people. He said that it was known among 
the peasantry as mal d'Aerouse, but the description caused Roussel 
to doubt the correctness of the diagnosis, as there was evidence 
to show that two diseases were confused. These two were pellagra 
and a palmar psoriasis, and again there was another condition 
which was a fusion of the two. Pellagra was found not only 
under the name mal d'Aerouse, but also as mal de Bascons, mal 
de Saint Amans, and mal de Sainte-Rosa. Mal de Saint Amans 
was derived from a statue in Bascons to Saint Amans which was 
always damp and sweating and this sweat was collected to be 
applied as a remedy to the affected part. It was thought by some 
that the term was a corruption of mal des Saintes-Mains and had 
nothing to do with the statue to Saint Amans. This name was 
supposed to owe its origin to the fact of the prevalence of the 
skin lesion on the backs of the hands. 



26 A TREATISE ON PELLAGRA 

The name mat de Sainte-Rosa was derived from a fountain of 
muddy water which existed at Ichoux and which was dedicated to 
Saint Rose. The water was supposed to have a curative effect 
on pellagrins. 

In 1846 Lachaise wrote of the presence of pellagra in the form 
of an epidemic in Pologne in Itoumania and attributed it to the 
introduction from abroad of bad maize. 

In 1858 Julius Theodori reported the occurrence of the disease 
in the provinces of the Danube. But it is interest ing to note in 
this connection that in 1847 ( 'aillet had written that he did not 
think pellagra occurred in the provinces of the Danube, but he 
found in Moldavia " a new disease," which was designated leprc 
endemique, but which, according to the description given by him, 
was certainly pellagra. 

Theodori's observation regarding the presence of pellagra in 
Moldavia was based on an observation made in 1856, to which he 
added the experience of his father and other physicians of the 
country. 1 He considered it a new disease due to agricultural and 
economic changes which had brought about the substitution of 
imported maize for the wheat and other forms of food used for- 
merly. In this work he showed that maize was first introduced 
into Europe in 1710 by the Prince Nicolas Maurocordato, ante- 
dating the introduction by Serban Cantacuzene, though the latter 
is usually given the credit for it. This latter introduction was 
not made until about the middle of the eighteenth century. He 
said that in his country there were no pathologic results for nearly 
a century. During this period no mention is made of the disease, 
either by the profession or by travelers. It was not until about 
1830 that Boerensprung, following Theodori, wrote on this subject. 

Sporadic cases of pellagra occurred in Vienna, according to 
Nicolas and Jambon, 2 as early as 1791. It is a notable fact that 
Billod first attracted attention to what he called pseudo-pellagra 
in the insane institutions and showed that it was the same disease 

1 De Theodori, Julius, " De pellagra — Dissertatio Inauguralis Medica." 
- J. Nicolas and A. Jambon, " Contribution de la Pellagra et du Syndrome 
pellagreux." Annates de Dermatologie et de Syphilographie, 190S. 



HISTORY AND GEOGRAPHICAL DISTRIBUTION 27 

as true pellagra. He first found it in the insane institutions of 
Rennes and Sainte-Gemmes, and later he discovered it in the 
asylums of Dijon, Nantes, LeMans, Mariville, Quimper, and Par. 

In recent years pellagra has been described in Mexico by 
Bouchard, and it has occurred in Brazil, Argentine Republic, 
Uruguay, and also in Africa. Sporadic cases have occurred in 
the Tyrol, Servia, Bulgaria, Greece, Asia Minor, and one case 
in England. Even more recently a sporadic case was discovered 
in the Shetland Islands. 1 Pellagra under the name psilosis pig- 
mentosa was described about 1889 occurring in Barbadoes. 

It has often been hinted by writers that the disease occurred 
among the American Indians prior to European invasion. This 
suspicion probably owes its origin to Strombio's statement that 
these people were very subject to sundry skin diseases. Probably 
the most authentic writer on the North American Indian was 
John Brickell, M.D., author of " The Natural History of North 
Carolina, with an Account of the Trades, Manners, and Customs 
of the Christian and Indian Inhabitants, etc." This work was 
published in Dublin in 1737. The writer was deputed by the 
government of the colony on several missions to the Cherokee tribe 
of Indians, and he has written a very full account of the diseases 
which he found among them at that time and which were known 
to the natives to have occurred in the past. It is probably in this 
work that we read the first reference in American medical litera- 
ture to that all-absorbing topic of the present day among the 
physicians of the southern states, hook-worm disease. He de- 
scribed this condition under the term Cachexy and its symptoms 
were given as follows : " The Face is very pale and discolor'd, 
and the Body big and swoln, this Distemper is principally owing 
to their eating great quantities of Fruit that this Country pro- 
duces, and to a sedentary way of living, and their eating Clay and 
Dirt which the Children, both White and Black, and some of the 
old People are very subject to, etc." This disease was declared 
very prevalent. The only cutaneous diseases mentioned are 
" Rashes and Prickley-heat, Tetter, and Ring Worms." He 

1 London Practitioner, 1909, 



28 A TREATISE ON PELLAGRA 

speaks, however, of yaws and describes it as a disease not well 
known in Europe, but very common here. He said it was like 
lues venera " having most of the symptoms that attend the Pox, 
such as Nocturnal Pains, Botches, foul Eruption, and Ulcers in 
several parts of the Body. . . . This distemper though of a 
venereal kind is seldom cured by Mercurials, as I have often 
experienced, for I have known some to undergo the Course of 
three salivations to no purpose, the virulency still continuing as 
bad as ever." His remedy was an infusion of the bark of the 
Spanish oak, the bark of the pine and sumac root. One might 
infer that a disease mistaken for syphilis which did not respond 
to mercurial treatment having the above-mentioned symptoms 
and for the relief of which astringents were used might be re- 
garded as pellagra. The astringents would hardly have been in 
order for any other condition except diarrhea, which does not 
occur in syphilis, but which is seldom absent in pellagra. How- 
ever, the assumption on this slim evidence of the real condition 
having been pellagra would not be justified. It seems reasonable 
to suppose that had pellagra existed in Xorth Carolina then as 
it exists now, this very observant writer would not have overlooked 
it nor could he have escaped its detection, though at that time 
the disease had not been described nor the name coined. It is 
reasonable to suppose that the disease did not exist at that time 
in this particular colony at least. 

It is altogether likely that the malady occurred sporadically 
in America for many years before its earliest detection. The most 
interesting fact in this regard was told me by Dr. Ch. Wardell 
Stiles. He says that he feels confident that the cause of the 
terrific death rate among the Federal troops imprisoned in the 
Confederate prison at Anderson ville, Georgia, was hookworm dis- 
ease and pellagra. Dr. W. J. W. Kerr of Corsica, Texas, is 
first hand authority for this opinion. The matter was carefully 
studied by Stiles, who thinks that it should vindicate the Con- 
federacy from the charge which has been frequently made that 
the Federal troops were starved to death while the Confederates 
doing guard duty at this time were not affected, though it 






HISTORY AND GEOGRAPHICAL DISTRIBUTION 29 

has been shown that they received the same fare as did the 
prisoners. 

In 1864 Dr. John Gray of Utica, New York, reported a case 
of pellagra. Doctor Tyler, of Somerville, Massachusetts, in dis- 
cussing this case referred to a similar one of his own. Both these 
cases were in the insane. It is said that an epidemic of a disease 
strongly simulating pellagra occurred in an asylum for the in- 
sane in Nova Scotia. This outbreak was reported by J. de Wolff. 
It is claimed that pellagra was diagnosed in the South Carolina 
Asylum for the Insane at Columbia in the early seventies by 
H. N. Sloan, but no report or record was made of it. Certainly 
the scourge existed among the inmates of this institution in the 
eighties, but it was attributed at that time to burns by sun or 
fire. D. S. Pope says that at least two cases occurred in the 
South Carolina penitentiary in the middle eighties. 

In 1883 Sherwell of Brooklyn reported pellagra in an Italian 
sailor. In 1889 Bemis of ISTew Orleans left a written diagnosis 
of a case in a white woman at the Charity Hospital in that city. 
In that year a case * occurred in North Carolina in the practice 
of the late Thos. R. Mask of Wilmington. It was diagnosed 
at the time as a form of psoriasis, but in 1907, when a large 
number of cases occurred in this same section, Doctor Mask de- 
scribed the case and I was convinced that the condition was none 
other than pellagra. 

In 1893 Sandwith noted the occurrence of pellagra in Egypt 
and, becoming interested in the geographical distribution, he 
wrote to many physicians in the United States, but was unable 
to elicit any evidence of its presence at that time or the history 
of any past occurrence. 

In 1902 Sherwell reported another case and H. F. Harris of 
Atlanta reported a case of anchylostomiasis presenting all of the 
typical symptoms of pellagra and which was an undoubted case. 

Nineteen hundred and seven saw the first real scientific work 
on the subject in this country, and this year will stand out in 

1 Bellamy, R. H., and Wood, E. J., " Pellagra in North Carolina." Bulletin 
State Board of Health. 



30 A TREATISE ON PELLAGRA 

the medical history of this country as one of the most noteworthy, 
for then it was that this great scourge, which had been a known 
curse of Italy for over a century and a half, became a problem 
of vastest importance equaling in the southern states the problem 
of tuberculosis. Probably no medical subject lias ever produced 
such profound interest on the part of the medical profession as 
did pellagra at that time and ever since. The man whose name 
will ever be connected as the discoverer of the existence of the 
disease in this country is George II. Searcy, who reported an 
epidemic occurring at the Mt. Vernon, Alabama, Insane Insti- 
tution for Negroes. The cases were carefully studied by him, and 
also by E. L. McCafferty of the staff of this hospital. They were 
assisted by E. D. Bondurant of Montgomery and [sadore Dyer of 
New Orleans. This report embraced an account of eighty-eight 
cases with a fatality of fifty-seven. In this same year, 1907, 
J. T. Searcy reported nine cases from the Bryce Memorial Hospital 
in Alabama. Again, in this year, T. C. Merrill reported a 
sporadic case from Texas. The importance of Searcy's work can 
hardly be overestimated. Through the help of his report in the 
Journal of the American Medical Association within a few weeks 
the disease was recognized in half a dozen states and its identity 
with Italian pellagra irrefutably established. Our increasing 
knowledge of the disease brought about by a wider experience 
has added little to the description of Searcy. This observation 
was accurate and complete. 

Before the appearance of Searcy's epoch-making report I pre- 
sented to the American Medical Association in 1907 an account 
of a condition which I considered a symmetrical gangrene of the 
skin occurring in an insane man. To my mind the really re- 
markable condition in this case was a coincident infection with 
both tertian and quartan malarial parasites. This combination 
was practically unknown, no case having occurred of the kind 
in this country, though I was able to find a report of one case 
in Turkestan. The publication of this article brought forth many 
letters of inquiry from many quarters of the South, and by the 
help of these men, who had observed the same condition, the 



HISTORY AND GEOGRAPHICAL DISTRIBUTION 31 

diagnosis was determined. I was especially indebted to Searcy 
for his kind letter showing me my error and proving conclusively 
that the condition which I had ascribed to malaria was true 
pellagra and that the malaria was merely a coincidence. 

In reading the " Proceedings of the Pan-American Medical 
Congress " for 1893 I recently found several diagrammatic cuts of 
a skin lesion and a number of water colors of a tongue condition, 
both of which were characteristic of pellagra. This article was 
entitled " Psilosis pigmentosa " and the author was Cuthbert 
Bower. To quote his opening paragraph : " During the past four 
years I have seen so many cases of chronic diarrhea — often end- 
ing fatally — in which a peculiar inflammation of the mucous 
membrane of the mouth is accompanied by a clearly denned pig- 
mentation of the dorsal aspects of the hands and feet, that I have 
been forced to the conclusion that this triple association is not 
an accidental one, but is pathognomonic of an epithelial disease 
sui generis, possibly peculiar to Barbadoes, or else closely allied 
to a specific disease of the alimentary tract which has its habitat 
in the East Indies and has been accurately described by Thin 
of London as ' psilosis linguae et intestinae.' " He said that the 
Dutch physicians of Java recognized the condition as possessing 
characteristics sufficiently unique to distinguish it from the ordi- 
nary chronic diarrheas and dysenteries prevalent in tropical 
countries and gave it the name " sprue," a term also employed 
in certain parts of Scotland to designate aphthous stomatitis. 

C. G. Manning, 1 medical superintendent of the asylum at 
Bridgetown, Barbadoes, reported in 1909 that for fifteen years 
there had occurred in the colony a disease generally called pellagra, 
but he rejected the diagnosis because it occurred only among the 
inmates of his institution and not among employees, though fed 
from the same kitchen. Hence the food, but more especially the 
maize, could not be accounted the cause, and he considered dam- 
aged maize the sole cause of the disease pellagra. His second 
objection was that the dark discoloration did not appear over 
the face, chest, and back, nor was it a true pigmentation in any 

1 Trans. Nat. Pellagra Cong., 1909. 



32 A TREATISE ON PELLAGRA 

sense. The third objection was that the eruption appeared and 
disappeared without leaving a mark. The interval of reappear- 
ance according to him was variable, but his most emphasized point 
was that it was not a true pigmentation. lie claimed that he 
named the disease psilosis pigmentosum, and described it, claiming 
that it was not pellagra. His description is a very exact one of 
the condition which we understand to be pellagra in the southern 
states, differing in no essential detail, and is merely another one 
of the many good reasons for a hesitation in accepting the maize 
theory of the causation of pellagra. 

As stated before, pellagra was found in Egypt by Sandwith in 
1893. i Warnock stated that the disease was spread throughout 
Eg'JPt D J the use of bad maize and that only a portion of the 
fellaheen became insane. There were many cases in the asylum 
at Cairo, but this was not a fair estimate of the extent of the 
disease in the country. He further noted at this institution cases 
of insanity produced by pellagra. 1 From his annual report we 
glean the following information in the form of a table. 

Year Men Women Total 



1896 


9 


2 


11 


1897 


10 


13 


23 


1898 


10 


29 


39 


1899 


19 


14 


33 


1900 


8 


27 


35 


1901 


27 


10 


37 


1902 


23 


10 


33 


1903 


41 


11 


52 


1901 


38 


15 


53 


1905 


51 


11 


65 


1906 


16 


13 


59 


1907 


69 


20 


89 


1908 


71 


17 


88 


1909 


68 


33 


101 




493 


225 


718 



1 " Pellagra," by Marie, both in tbe original and also the translation by 
Lavinder and Babcoek. Columbia.. S. C, 1910. 



HISTORY AND GEOGRAPHICAL ' DISTRIBUTION 



33 



This table shows the number of cases under observation. It is 
interesting to compare it with the table below which shows the 
number of deaths during a part of the same period. At the 
Kasr-et-Nil Hospital, Cairo, Marie * says there were in ten years 
more than one thousand cases. Many of these cases — about forty 
yearly — are committed to the asylum at Abbassia on account 
of a resultant insanity. Sandwith thought that about 36 per cent 
of the Egyptian peasantry were affected. The proportion in 
better conditioned neighborhoods falls to 15 per cent, but else- 
where rises to as much as 62 per cent. In upper Egypt the 
dryness of the atmosphere and the use of millet in place of maize, 
according to Marie, has made the danger much less. 

Deaths from Pellagra at the Cairo Asylum 



Year 


Men 


Women 


Total 


1901 


6 


4 


10 


1902 


6 


2 


8 


1903 


9 


1 


10 


1904 


3 


3 


6 


1905 


13 


4 


17 


1906 


9 


1 


10 


1907 


.. .. 7 


2 
2 


9 


1908 


6 


8 


1909 


10 


5 


15 




69 


24 


93 



R. H. Bellamy of Wilmington and J. B. Wright of Lincolnton 
were the first physicians in North Carolina to recognize pellagra. 
Bellamy made his first diagnosis prior to the appearance of 
Searcy's article, but his report was not read until 1908 before 
the American Medical Association. 2 To him I am indebted for 
the first sight of the disease. His first cases, five in number, 
were studied in 1905, though we did not identify the condition 
with pellagra, as we had always been taught that this disease 
did not occur in this country. Long before we learned the cor- 

1 Marie, A., "La Pellagra," Trans, by Lavinder and Babcoek. 
- Bellamy, R. H., " Pellagra." Jour. Am. Med. Assoc, 1908. 



34 A TREATISE ON PELLAGRA 

rect name we were entirely familiar with the disease picture 
and especially with the prognosis, for at that time there were 
no recoveries except exceptionally, as the disease assumed the 
acute form, about which there will be a later mention. 

In 1908 J. J. Watson and J. W. Babcock of Columbia, South 
Carolina, went to Italy and investigated pellagra in order to 
prove or disprove the identity of the disease in the United States 
with that of Italy. They were thoroughly convinced that there 
were no points of difference. Prior to this Babcock x had written 
a report in the form of a query regarding the outbreak of pellagra 
in the South Carolina Institution for the Insane at Columbia. 
In this paper the suggestion was made that pellagra did exist in 
the institution. This article was published in several different 
places and attracted world-wide attention. Much credit is due 
Babcock for his enthusiastic work in bringing this disease before 
the attention of the American medical profession, to whom it 
was entirely unknown, even theoretically. To his activities are 
due the various movements which resulted in the establishment 
of the National Pellagra Conference, which meets yearly, and 
already through its two meetings has done much to promulgate 
a better acquaintance with this great scourge. 

In 1908 C. H. Lavinder of the United States Public Health 
and Marine Hospital Service stationed at Wilmington, North 
Carolina, had his attention for the first time directed to the 
disease. Through the courtesy of the local physicians he was 
given an opportunity to see a number of cases. At that time 
these men were thoroughly acquainted with pellagra, having had it 
in their midst since 1905, and they had collected valuable data 
not only from abundant clinical material, but also from the foreign 
literature. At that time there was no literature on this subject in 
English, but they had for their own use made a few translations, 
chief among which was the work of Tuczek. On reporting the 
existence of this disease to the late Surgeon-General Wyman 
Doctor Lavinder was at once ordered to prepare a precis for im- 

1 Babcock, J. W., Report, S. C. Board of Health, 1907, and Am. Jour, of In- 
sanity, 1907. 



HISTORY AND GEOGRAPHICAL DISTRIBUTION 35 

mediate publication. This paper was largely the gleanings from 
the work of Procopiu in French and the above-mentioned work in 
German. In the meanwhile one patient with the disease was 
admitted to the Marine Hospital at Wilmington. This precis 
was very generally distributed and constituted one of the first 
authentic publications in this country. Through it the matter 
was brought officially to the attention to the profession, the 
public, and most important of all, to the United States Public 
Health and Marine Hospital Service, which since that time has 
done a great deal of valuable work on the subject and proven 
to many the great importance of this great strong arm of the 
national government. 

In 1908 the South Carolina Board of Health held a con- 
ference on pellagra, and in November, 1909, a national con- 
ference was held in Columbia under the same auspices. 

In 1909 it was estimated that at least one thousand cases of 
pellagra occurred in sixteen states, and it was conservatively esti- 
mated that fifteen hundred cases had occurred in the southern 
states since 1906. In 1910 the malady was suspected or shown 
actually to occur in thirty-three states, and the number of cases 
approximated three thousand and a total of five thousand had 
occurred in five years. Foci of the disease were discovered in 
insane institutions of Alabama, South Carolina, Georgia, North 
Carolina, Florida, Louisiana, and Virginia. 

The pathologic study of the nervous system in pellagra made 
by H. A. Cotton, superintendent of the New Jersey Hospital 
for the Insane, has opened up a most interesting field of specu- 
lation and study. The findings thus far have led him to think 
that it is not improbable that the disease has occurred in northern 
institutions unrecognized for many years. In a personal com- 
munication from H. A. Hurd of the Buffalo Hospital for the 
Insane I was impressed with the possibility that there was pella- 
gra in his institution under the diagnosis of general paralysis 
of the insane. In 1906 I showed my photographs of pellagra to 
Doctor Hurd and he suggested this explanation of the matter. At 
that time I did not know that the condition was pellagra and I 



36 A TREATISE ON PELLAGRA 

do not now know what Doctor Hurd's present views are. He in- 
formed me that such a skin lesion as shown in my photographs 
was not uncommon in his paretic cases. I met this same ex- 
perience in the North Carolina State Hospital for the Insane. 
A patient of mine was sent home from that institution on leave. 
I was curious to know the reason for her wearing cotton gloves, 
and on inquiring was told that her hands were sore. An ex- 
amination showed not only the typical symmetrical erythema, but 
also the characteristic tongue and diarrhea confirming the diagnosis 
of pellagra. Through the courtesy of James McKee, superin- 
tendent of the institution, as well as his carefully kept clinical 
records, the fact was demonstrated that pellagra had existed in 
the hospital for a number of years and had been counted merely 
an occurrence with dementia paralytica. In this same connection 
it is interesting to note the occurrence in the Cook County, Dun- 
ning, Bartonville, and Peoria, hospitals for the insane. Since 
that time much important work has been done in Illinois. In 
June, 1910, J. D. Long of the United States Public Health and 
Marine Hospital Service verified the diagnosis in nine cases in 
the Philadelphia General Hospital (Blockley). 

Special commissions for the study of pellagra have been ap- 
pointed by the United States Public Health and Marine Hospital 
Service, by the governor of Illinois, by the Xorth Carolina Board 
of Health, by the Tennessee Board of Health, and by the Xew 
York Postgraduate Medical School. This latter institution is 
about to establish a field laboratory for the more intimate study 
of the disease. At this writing L. M. Sambon of the London 
School of Tropical Medicine with a number of interested workers 
is in the Austrian Tyrol under a "Wellcome grant experimenting 
with the Simulium reptans as the intermediate host in the trans- 
mission of the disease. This hypothesis which will be again re- 
ferred to was promulgated by Sambon in 1905 before the British 
Medical Association and since that time has grown rapidly in 
favor. 

Throughout the South pellagra is the live topic of medical 
interest, and rightly so, for it has become as great a problem as 



HISTORY AND GEOGRAPHICAL DISTRIBUTION 37 

it has been in Italy since Strombio reported it in 1784. The 
disease is either on the increase or else is being more generally 
recognized, and already two special institutions for its treatment 
have been established. In North Carolina, at least, it is second 
only to tuberculosis in importance. One town of twenty-five thou- 
sand in this state has already reported two hundred cases. In 
1909 I made a statement before the North Carolina Nurses Asso- 
ciation that there were in that state one thousand cases. This 
statement was made the object of ridicule by the press of the state, 
who refused to accept this unpleasant fact. Only a few months 
later the Board of Health estimated the number at three thousand. 
It is thought by many that at this time the number would be 
much nearer ten thousand. 

In Roumania in 1901 there were 33,645 cases; in 1905, 54,689 
cases ; in 1906, more than 100,000 cases. It is stated by Marie, 
from whom these figures are taken, that only three cases occurred 
in Bucharest, and that the disease is largely confined to country 
districts, accounting, according to this author, for the high in- 
fantile mortality. It is further stated that the staple food of the 
peasantry is maize and the 1909 crop was 126,000,000 bushels. 
Of course, the cause of the disease is ascribed to the use of this 
form of food. 

In 1882 Marie said that Henry Strachan, senior medical officer, 
reported 510 cases of what he called malarial multiple peripheral 
neuritis, which he observed in the Kingston, Jamaica, Public 
Hospital. The patients complained of numbness and burning 
heat in the palms and soles, often accompanied by cramps which 
were worse at night and in bad weather. Impaired hearing and 
vision with a feeling of constriction around the chest were re- 
ported. There was an eczema of the eyelids, # the angles of the 
mouth, and the mucocutaneous margins of the nostrils. Pain in 
the hands and feet was noted. There was notable emaciation. 
Pigmentation of the palms, soles, and lips occurred. When death 
occurred it was due to respiratory paralysis, but this was ex- 
ceptional, as the disease was comparatively trivial. The sub- 
jective symptoms are summarized thus : dimness of vision, im- 



38 A TREATISE ON PELLAGRA 

paired hearing, numbness and cramps of the extremities, girdle 
pains, and joint pains. The objective symptoms are: trophic 
changes, monoplegias, altered gait, the knee jerk absent in over 
one-half, exaggerated or subnormal in 2o per cent, and normal 
in the remaining cases, cutaneous reflexes varied greatly, sensation 
blunted or absent, soreness of the mucocutaneous lines of junc- 
tion, and wasting of the muscles. Soreness of the mucocutaneous 
borders of the eyelids, lips, urethra, anus, or vulva were among 
the first symptoms. Wasting and contraction of the muscles oc- 
curred in extreme cases and the result was the "claw" hand or 
foot. There was some retinal hyperaemia, seldom enough to be 
counted as optic neuritis, but there was pigmentation of the 
fundus. Pigmentation of the brain and the spinal cord were 
the only changes noted post mortem. Strachan thought the con- 
dition was due to malaria, but this view has not been generally 
accepted. 

Braddon in speaking of food poisons said: " Another disease 
probably owning similar etiology is Strachan's disease occurring 
among the natives of the West Indies, which in some respects 
resembles pellagra. The West Indians live largely, too, on 
maize." 

Sandwith in a private letter referred to in Lavinder and 
Babcoek's translation of ^Marie's work, which has been freely 
drawn on for this data, says that Strachan did not describe either 
beri-beri, multiple neuritis, or pellagra, but that it is possible that 
the condition is post-dysenteric neuritis, of which there is a great 
deal in the West Indies. The nervous symptoms are very different 
from those of pellagra, in which condition there is not the uni- 
formity of symptoms as Strachan described. It would be equally 
as well in order to consider acrodynia as pellagra in this con- 
nection. Sir Patrick Manson says it differs from beri-beri in the 
absence of edema, and he does not think that it can be ascribed 
to malaria, but is more likely a specific disease entity in itself. 
It is interesting to note the confusion regarding the classification 
of this condition, and one is made to think that if such doubts 
can arise at this time of great medical advancement it is not to 



HISTORY AND GEOGRAPHICAL DISTRIBUTION 39 

be wondered that the early observers often experienced difficulty 
in their classifications. 

Wollenburg of the United States Public Health and Marine 
Hospital Service, reporting to his department from Naples, 

says: 

" Pellagra, despite the extensive interest which is being taken 
in its suppression, continues to spread in certain regions of Italy. 
A vigorous campaign has been waged against the disease for a 
number of years, laws concerning it have been enacted, improve- 
ments in grain culture have been encouraged, sanitation has been 
widely improved ; the number of pellagrins, however, is diminish- 
ing but slowly. The sum total which is annually • expended for 
salt, proper food, and hospital accommodations for the care and 
treatment of the poor affected with pellagra is enormous. During 
the past twenty-five years the, extent of the disease has lessened 
considerably in the northern part of Italy — Piedmont, Lombardy, 
Venetia, and Emilia — while there has been a persistent spread 
in central Italy, very notably in Tuscany, Marches, and Umbria. 
The disease is now appearing in alarming proportions in Latiimi 
and in Abruzzo and Molise, compartments in which it was un- 
known some years ago. What is more striking is that the disease 
invaded southern Italy in 1908, cases having occurred in the 
vicinity of Naples and in Calabria. At present pellagra appears 
to be firmly established in the lower as well as in the upper por- 
tion of the Italian peninsula. The reason for this better showing 
in the north is not altogether plain, but it is partly attributed to 
the economic, social, and sanitary improvements that have been 
effected there in recent years. In the last triennium the disease 
was markedly reduced in the provinces of Arezzo, Bologna, Bres- 
cia, Florence, Forli, Macerata, Mantua, Modena, Padua, Pavia, 
Perugia, Pesaro, Rovigo, Treviso, and Venetia. An increase took 
place in Bergamo, Milan, and N/ovara. Statistics for central 
Italy show marked improvement in the province of Perugia. 
For the rest, the status remains nearly unchanged. In south- 
ern Italy there are new cases in the provinces of Avellino and 



40 A TREATISE ON PELLAGRA 

Cosenza. In the same period the total number of new cases 
reported for the whole country has been gradually reduced as 
follows : 

New Cases New Cases 

1906 6783 1908 2766 

1907 5307 

" The total number of pellagrins in Italy at the present time 
may be estimated at less than 50,000. Considering that during 
the years 1906 and 1907 pellagra was the cause of 1873 deaths 
and 1293 cases of insanity, together with the long duration of 
the illness and its effect on the earning capacity of the afflicted 
individuals, the above figures are sufficiently startling. 

Total Number of Pellagrins by Census 

1879 97.855 1899 72,603 

1881 104,067 1905 55,029 

" The mortality seems to be lessening. It changed very little 
after the law of 1902 came into effect until the years 1906 and 
1907, when there was a fall in the number of total deaths to less 
than one-fifth of those during the preceding years. 

Total Deaths from Pellagra in Italy 

1898 3987 1903 2647 

1899 3836 1904 2363 

1900 3788 1905 2357 

1901 3054 1906 437 

1902 2376 1907 376 

" The hoped-for results and salutary intent of the law — to pre- 
vent the consumption of maize of poor quality — have hardly been 
realized. The law permits the milling of low grade maize in case 
it is not to be used as an aliment for man, but this provision is 
held to be hard to enforce, proper sanitary supervision being very 
difficult." 



HISTORY AND GEOGRAPHICAL DISTRIBUTION 41 

Number of Pellagrins in Compartments by Census x 

1881 1889 1905 

Piedmont 1,328 1,223 1,012 

Liguria 56 30 56 

Lombardy 36,630 19,557 15,746 

Venetia 55,881 39,882 27,781 

Emilia 7,891 4,617 3,357 

Tuscany 924 1,125 1,137 

Marches 406 920 1,436 

Umbria 872 5,103 4,250 

Latium 32 146 195 

Abruzzo and Molise 59 

A correspondent of the American Medical Association 2 from 
Vienna wrote the following interesting letter, which was repro- 
duced by Lavinder and Babcock: 

" In the eastern part of the Empire a disease has been very 
prevalent among the poorer classes for some years past which has 
proved puzzling to the profession. The clinical symptoms some- 
what resembled those of lepra, but differed in not having the 
anesthetic patches, with consequent dystrophic destructive pro- 
cesses. Profound cachexia with gastrointestinal disturbances are 
generally observed after the disease has persisted for from 
twelve to eighteen months. In many instances these were the 
only symptoms, while in other cases circulatory disturbances 
are a prominent feature. Similar cases were reported from 
neighboring districts of Russia and Roumania, and many 
scientists studied the disease. It was finally agreed by the 
majority of the investigators that the cause of the condition lay 
in the food. The peasants live largely on maize, making bread 
and other foods out of this material ; a dish called ' polenta/ con- 
sisting of coarsely ground maize with lard, is partaken of heartily 
daily. In certain wet years the corn was affected by a sporidium 
and became still more unwholesome because of the presence of 

1 Lavinder and Babcock's Trans, of Marie's " La Pellagra." 

2 Journal Am. Med. Assoc, Aug. 1, 1908. Lavinder and Babcock's transla- 
tion of Marie's work, p. 61. 



42 A TREATISE ON PELLAGRA 

certain toxic substances which are held responsible for the disease 
just described — pellagra. In the province mentioned, inhabited 
by 1,500,000 people, there are over 38,000 cases reported (3 per 

cent)." 1 

The above-mentioned correspondent a little later again wrote: 

" Since 1905 the action of the government in suppressing pella- 
gra has been going on and including all affected areas. Alto- 
gether a population of 2,250,000 has been investigated with the 
result that about 78,163 persons (3 per cent) were found to be 
suffering from one form or another of the disease. Certain dis- 
tricts were more affected than others, and, as a rule, the poorer 
classes succumbed more easily than those who could procure the 
food regarded as necessary. The measures of the government have 
been of a prophylactic nature." 

Lavinder and Babcock give the following interesting account 
of pellagra in Transylvania : 

" An account of pellagra in Transylvania is given in the Lancet 
of July l(i, 1898, p. 164. Transylvania is in the Carpathian 
Mountains, on one side being inhabited by Hungarians, on the 
other by Roumanians — the descendants of Roman legionaries of 
the time of Trajan and his successors. 

" When an endemic outbreak was reported from Transylvania 
a commission was appointed and confirmed the diagnosis of pella- 
gra. But fifteen years previously Doctor Takach reported sus- 
picious cases of skin diseases which he named pellagra, but this 
diagnosis was questioned by a dermatologist of Budapest. In 1897, 
however, special orders were issued to hospitals and asylums to be 
on the lookout for pellagra. Doctor Takach was the first to send 
in a patient suffering from pellagra. After that numerous cases 
were found. The disease was thought to be the result of insuffi- 
cient nourishment, aggravated by bad hygienic conditions and 

1 Jour. Am. Med. Assoc, Sept. 4, 1909. See also Lavinder and Babeoek's 
translation of Marie. 



HISTORY AND GEOGRAPHICAL DISTRIBUTION 43 

malaria. No cases could be detected where the people had good 
and sufficient food. The disease seemed to follow continuous 
rains, bad crops, and murrain among the flocks." 

In 1910, in a consular report, Vice-Consul W. Bayard Cutting, 
Jr., at Milan said that in 1770 pellagra was almost unknown in 
Italy, but that in 1839 in Lombardy alone there were over 20,000 
and in 1879 over 40,000 cases. In 1881 the provinces of Pied- 
mont, Lombardy, Liguria, Venetia, Emilia, Marches, Umbria, 
Tuscany, and Lazio having all told a population of 16,689,735 
contained 104,067 victims of the disease. These figures cannot 
represent all cases because of defective reports, and yet even this 
represents one case to every sixty of the rural population, while 
in such regions as Venetia away from the agricultural district 
the proportion was only one to nineteen. He claimed that the 
spread of the disease was confined to those regions where maize 
formed the chief food. Maize, according to this observer, was 
introduced into Italy from the Balkan States. 

In this same report 1 Babcock has collected some very impor- 
tant data regarding the distribution of the disease. While it will 
be noted from his table that the disease is much more prevalent 
in the southern states the fact can not be lost sight of that the 
disease is generally distributed and deserves more of the attention 
of the profession generally than has hitherto been accorded to it. 
From what has been said on a previous page it will be recalled 
that there is some ground to suspect that an atypical form of the 
disease has been occurring for some years in the northern insti- 
tutions for the insane and that this matter deserves more attention 
and study than it has received. 

1 " Prevalence of Pellagra," by J. W. Babcock and W. Bayard Cutting. Pub- 
lic Document No. 706. 



44 A TREATISE ON PELLAGRA 

Prevalence in the United States 1 

Massachusetts 3 Tennessee 51 

New York 3 Kentucky 5 

New Jersey (imported) 1 Illinois 250 

Pennsylvania 33 Iowa 2 

Maryland 7 Kansas 2 

Virginia 100-300 California 7 

North Carolina 200 Indiana 1 ( ?) 

South Carolina . . 500 Ohio '. 1 

Georgia 670 Colorado 1 ( ?) 

Florida 50 New Mexico 2 

Alabama 330 Missouri 3 

Mississippi 188 Vermont 1 

Louisiana 500 ( ?) Rhode Island 1 

Texas 100 West Virginia 1 

Oklahoma 1 District of Columbia 1 

Arkansas 1 

Note. — Later reports of cases of pellagra have been made 
from Wisconsin, Washington, Michigan, and Oregon. Under 
date of October 3, 1911, a report was made to the Tennessee 
Board of Health by the commission appointed to study the disease 
in that state. This was probably the most complete work of the 
sort yet done in this country and is a great credit to that state. 
The report was based on an observation of three hundred and six- 
teen cases, though the committee estimate the number of cases in 
the state at twenty-five hundred. To quote the report in this 
place would not be in order, as it will be referred to at length 
later, but the tables are of much importance and a number are 
here given. 2 

Number of counties in the State 96 

Number of counties visited 61 

Number of counties found with pellagra 58 

Number of counties with pellagra not visited 9 

Total number of counties with pellagra 67 

Number of detailed reports on file 316 

1 Babcock, J. W., " Prevalence of Pellagra." Consular Report No. 706, 
Washington, 1911. 

2 "Pellagra: Report upon 316 Cases of this Disease as submitted by the 
Commission Appointed by the Tennessee State Board of Health." 



HISTORY AND GEOGRAPHICAL DISTRIBUTION 45 

Total Cases 316 

Male Whites 98 Male Colored 4 

Female Whites 200 Female Colored 14 

With each day comes news of further extension of the scourge 
and it seems that the conditions in the United States are as favor- 
able as in Italy, where the disease has done so much to retard 
the progress of that country. The question is one that should 
engage the attention not only of the medical profession, but of the 
public generally. 

It is possible from what has gone before that the reader will 
agree with me that pellagra was probably an ancient disease ; 
that the proofs of its antiquity are fully as well established as 
those of its modernity. Sambon especially, among recent writers, 
is very positive from historical proofs that the disease was known 
many years — even centuries — before the introduction of maize 
into Europe. He brings out proof after proof that the older 
writers considered it a form of scurvy and shows that even the 
great authority, Marzari, whose writings have been of so much 
importance, proposed the name of " Italic scurvy." In his treatise 
on scurvy Delia Bona probably alluded to pellagra when he said : 
" Interdum, sed rarius apud nos cutis fmditur, asperi tudinemque 
habet, et squamas quasdam remittit sic ut ad eum morbum accedat 
quam graeci elephantiasim vocant." 

Regarding the probability of the overlooking of pellagra in 
earlier times Sambon wrote : 1 

" The previous non-recognition of this disorder is by no means 
surprising. The history of many other diseases in this respect 
is similar to that of pellagra. It would be idle to seek for descrip- 
tions of typhoid fever among the medical writings of antiquity 
or of the Middle Ages, and yet this disease was no new malady 
when definitely extricated in the eighteenth century from the old 
' fevres pestilentes.' The history of rickets is just as obscure 
prior to Whistler's thesis (1645) and Glisson's famous treatise; 

1 Sambon, L. W., Progress Report on the Investigation of Pellagra. Reprint 
from The Journal of Tropical Medicine and Hygiene, 1910. 



46 A TREATISE ON PELLAGRA 

yet it would be a great mistake to believe that the so-called ' mor- 
bus puerorum Anglorum ' appeared as a new disease at the begin- 
ning of the seventeenth century and broke out for the first time 
in the English counties of Dorset and Somerset. Scarlet fever 
was not recognized as a distinct disease before the seventeenth 
century, when the works of Sennert, Doering, and Sydenham crys- 
tallized the medical comprehension of this morbid process. It 
would be absurd to believe in any of the dates assigned to the 
first appearance of this disease in the various European States. 
In all probability it had long existed, but had always been con- 
founded with measles. Scurvy is another disease, the history of 
which does not go further back than the fifteenth century, when 
it was brought prominently to notice by the havoc it played aboard 
ship, as in Vasco de Gama's great voyage round the Cape in the 
year 1497, when 100 out of a total of 160 men succumbed to it. 
Until a few years ago kala-azar was looked upon as a disease 
peculiar to Assam. The discovery of its causative agent by Sir 
William Leishman, in 1908, made the diagnosis comparatively 
easy, and the disease was soon reported from Ceylon, China, 
North Africa, Sicily, and other parts. Its late recognition in 
these places, however, does not in any way signify recent im- 
portation. 

" Returning to pellagra, it is interesting to notice that the 
disease was recognized in Egypt by Primer as early as 1847; 
but Primer's statements were discredited by Hirsch, and almost 
half a century elapsed before it was definitely proved, by Dr. 
Sandwith's investigations, that pellagra is one of the scourges of 
Egypt, and a very serious one among the fellaheen of the lower 
country. The case of the United States of America is again most 
instructive. Until quite recently all American text-books stated 
quite emphatically that pellagra was unknown in that part of 
the world; then suddenly the disease is discovered in no fewer 
than twenty-six states. This wide distribution of the disease, 
the diagnosis of a few cases as early as 1863 or 1864 in the 
JSTew York and Massachusetts asylums, and the absence of any 
definite history of recent importation or outbreak show very clearly 



HISTORY AND GEOGRAPHICAL DISTRIBUTION 47 

that the disease is of long duration in the United States, yet it 
escaped recognition. 

" A fact which powerfully suggests that pellagra could not 
have appeared for the first time in Italy about the middle of the 
eighteenth century, but that it must have been very ancient, is the 
wide distribution it had already attained at that time. Indeed, 
we know that it ranged throughout the north of Italy from the 
Julian Alps to the Alps of Piedmont, from Lago Maggiore to 
the Arno. I have already mentioned that Pujati saw the disease 
at Feltre about 1740, and that Nascimbeni a few years later 
recognized it in Friuli. Soler (1791) found it along the River 
Piave in the district of S. Polo, Sartogo (mentioned by Franzago, 
1791) in the neighborhood of Aviano, Aldalli (mentioned 'by 
Soler, 1791) near Sarone, a village at the foot of the Julian Alps. 
Fanzago (1804) states that Doctor Storni, who practised for over 
forty years in Campo S. Piero, Padua, had never observed any 
difference either in the number of persons attacked or in the 
severity of the disease. He believed that the malady could not be 
looked upon as of recent origin, since his predecessor, Doctor Carlo 
Barbanti, who had taken up residence in that district thirty 
years before him, about 1730, had stated that he had always 
observed it in those places. A work published in Naples in 1788 
under the title " De epidemicis et contagiosi morbis " mentions 
the existence of pellagra in the territory of Modena. Tarzaglii 
(1794) states that the disease had been noticed previous to 1730 
in the vicinity of Sesto Calende (on Lago Maggiore) ; Albera 
(1781) says: 'Doctor Brava, a man of repute and learning, has 
told me that pellagra had been known for over sixty years (1720) 
in the Ligurian mountains ; it proceeded in the same order, and 
manifested itself and grew with the same symptoms. . . .' 

" A sudden influx of literature on a newly described disease 
is not necessarily an indication of recent appearance or unusual 
prevalence. Speaking of typhoid fever, Hirsch says : ' This large 
amount of writing on typhoid, especially between 1830 and 1840, 
has given rise to the often expressed opinion, which at one time 
I shared, that we have to do with unusually general prevalence 



48 A TREATISE ON PELLAGRA 

of the disease during that period, or that its general diffusion had 
not been reached until recent times. I think, however, that we 
must consider this to be an erroneous view, and that we must ex- 
plain the phenomenal outburst of literature by the sudden and 
rapidly culminating interest of the profession in a new and im- 
portant object of study — a phenomenon which has recurred in 
the case of many other forms of disease.' 

" The sudden flood of American literature on pellagra and the 
recognition of the disease throughout the greater part of the 
United States since 1908, when Doctor J. W. Babcoek inculcated 
its grave importance, are but a repetition of what happened in 
Italy at the close of the eighteenth century." 



CHAPTEK II 

THEORIES OF ETIOLOGY 

The cause of pellagra is unknown, and, indeed, at the present 
time there is more uncertainty about the whole matter than ever 
before. For nearly two centuries and, in fact, since the time of 
the first known writer on the subject, Casal, maize or Indian corn 
has been the supposed cause. In the minds of most pellagrologers 
it would be as absurd to expect ergotism in one who had never 
eaten spurred rye as to expect pellagra to be due to any other 
cause than altered maize. But in the case of ergotism and spurred 
rye there is no contention, as it is an accepted fact by all observers 
without exception that there is one and only one cause, and there 
has been no contradictory evidence. The case of pellagra and 
damaged maize is different. Since the very first of our knowledge 
of pellagra there have been enthusiastic advocates of the maize 
theory, but there have also been those equally opposed to it. It is 
likely that the matter would have rested in this unsettled state, 
had it not been for the fact that such observers as Billod attempted 
to separate true pellagra, a disease in which the patient did eat 
maize, from false pellagra in which the patient did not eat it. 
The clinical description of false pellagra is absolutely the same as 
for the true and one cannot but feel that such a view is merely 
begging the question. It is my intention in this chapter to give the 
various theories without prejudice, but it is also my intention to 
show the lack of scientific accuracy which from the start has so 
largely characterized the study of the question. 

We are told that Casal in his description of Mai de la Rosa men- 
tioned maize as one of the probable causes of the disease. 

The elder Strombio was very positive in his opinion of the re- 
semblance of pellagra and scorbutus. He said that the country 



50 A TREATISE ON PELLAGRA 

people who were subject to the disease inhabited miserable damp 
rooms, and after the work of summer was done spent the time in 
great laziness without regard to cleanliness. He thought that such 
a manner of living was also responsible for scurvy, though he rec- 
ognized the fact that the two diseases were very distinct. He 
thought that moist air and dampness had a great influence on 
scurvy but emphasized the point that pellagra occurred in high, 
dry countries. 

Throughout the history of the scourge all writers have agreed 
on the one point, that workers in the earth living in rural districts 
are almost exclusively the class of people affected. Recently this 
fact has been made use of to aid in provi?ig the correctness of Sam- 
bon's hypothesis — that the disease is transmitted by a fly which 
is a field pest. It is notable that Albera and Odoardi found it in 
people leading a quiet, inactive life. My own experience does not 
altogether bear out the contention of Strombio, for I have found 
the disease well defined in merchants, professional men, women of 
the higher walks of life, and in people who lived well but did no 
work of any kind. 

The action of the rays of the sun was thought by Frapolli to be 
the sole cause and Gherardini, who had the same view, said that 
he produced opisthotonus in pellagra by allowing the victims to be 
exposed to it. But Frapolli thought he was dealing with a skin 
disease and in this he was mistaken. He thought that the internal 
manifestations were the result of the skin lesion and the severity 
of these symptoms depended on the severity of these local manifes- 
tations. At the present time the actinic rays of the sun are thought 
by some to be an exciting cause in the production of the erythema. 

Zanetti thought that bad food was a definite cause and also 
that the condition was favored by bad air and poor hygiene. 
Gherardini, who seemed to have the happy faculty of often chang- 
ing his views, is accredited with the opinion that it might be caused 
by the consumption of Turkish wheat (maize) or other damaged 
grains as well as by poorly cooked breads and the abstinence from 
wine among those accustomed to it. Albera opposed the view that 
bad bread or abstinence from wine was a cause, and advocated the 



THEORIES OF ETIOLOGY 51 

idea that the trouble was due to change of climate, neglect of the 
body, and the eating of flour, chestnuts, lentils, and poor quality 
of plant food. Odoardi thought that the lack of salt in the polenta 
was a cause. It should be remembered in this connection that salt 
was a government monopoly and often beyond the reach of the poor 
peasant. The mixture of rye and maize was named as a cause, 
as well as soft cheese made of goat's and cow's milk. Strombio said 
that, while the idea of bad food being the cause of the disease was 
generally accepted in his time, each observer had a special opinion 
of his own as to the exact character of this deficiency. As we fol- 
low the disease down through the years and finally see maize the 
only food stuff incriminated we find a repetition of this diversity 
of opinion though practically all were willing to unite on the gen- 
eral proposition. It is really interesting to enumerate the various 
views of the supposed noxiousness of maize. 

Strombio suggested the idea that possibly the seed of some 
noxious weed had become mixed with the grain. One of the old 
observers wrote thus : " The weather was bad and there grew much 
weeds among the wheat and many people had headache, and in 
summer ulcers, showing a bad condition of the fluids. I found 
several cases of pellagra among these people." 

Strombio, who wrote in 1784, stated that his predecessors sup- 
posed the cause lay in scanty and insufficient nourishment as a 
general cause, but he thought that this could not be a specific cause 
and mentioned a number of examples. He said that while some 
authors thought dry air, sudden changes of weather, and the hurt- 
ful action of certain plants were responsible, he found only that 
it was at home in poverty and bad hygienic conditions. He said : 
" I look into my case book and find that bad hygiene is the chief 
cause. People entirely healthy who develop intermittent fever also 
develop pellagra. Rachitic children and chlorotic girls were pecul- 
iarly susceptible. ... Several women previously healthy would 
develop the disease in pregnancy or during the puerperium. Pel- 
lagra has an infinite number of causes. Bad food is an important 
but not a sole cause and, finally no cause alone is likely to bring it 
forth." 



52 A TREATISE ON PELLAGRA 

Boerhaave described the disease and considered it due to certain 
disturbances of excretion. Odoardi, following out this theory, 
decided that it was due to the effect of certain abnormal acids in 
the system. 

Strombio considered the seat of pellagra to be in the 
stomach and thought he could prove his claim at autopsy. He 
said that this would easily explain the relation of the abdomen, the 
head, and the skin. Like Ramazini he thought that an accumu- 
lation of mucus in the stomach or lower bowel would explain the 
disease. 

Albera tried to find the cause by actual experimentation. To 
test the action of a strict vegetable diet he chose different groups 
of patients. All groups receiving bread and wine were relieved 
of the trouble for the time, though Albera concluded that it merely 
retarded the progress of the disease which would continue to recur 
in each successive spring. 

Vincenzo Sette thought that moisture caused a digestive disturb- 
ance resulting in pellagra. He did not think that the cause could 
be found in the climate. He said: " I have traveled through all 
sorts of country and have seen the habitations of both rich and 
poor, but regardless of this it is more prevalent in sandy regions. 
It also occurs in high countries where there is water and also where 
there is no water. An improvement of general hygiene causes a dis- 
appearance of the disease." 

Albera, Soler, and Sartago found a cause in poor ventilation. 

In 1832 Spesa x found a more definite and scientific cause in the 
" exhalation of ammoniac which comes from internal fermentation 
in the midst of which pellagrins live." Facheris and Gherardini 
always considered this theory unreliable. 

All the earlier writers tried to connect the appearance of the 
disease in country people with the etiology. It was thought that 
the exposure to the changing weather or the hard labor with a lack 
of sufficient nourishment might be contributory. Facheris wrote: 
" In these more recent years it is hard to see why the larger number 
of beggars, the artisans of both sexes but especially the weavers, 

1 Spesa, Anna Univ. di Medic, 1832, no. d'Oct. et Nov. Quoted by Roussel. 



THEORIES OF ETIOLOGY 53 

and others not exposed to the action of the sun or making their 
living by the earth, have pellagra." 

Toward the middle of the nineteenth century all writers adopted 
the idea that pellagra was a disease of malnutrition though it might 
affect the rich as well as the poor. 

Del Campo traveling in Pola de Siero saw Mai de la Rosa sud- 
denly appear among a people who ate much maize and grew it as 
well under a burning sun. He thought the appearance was the re- 
sult of the accumulation of heat in the blood. Fifteen years before 
this, Vay, while studying electricity, concluded that pellagra was 
the result of the abnormal accumulation of electric fluid in the 
blood. 

There were several to advocate a miasmatic theory of the causa- 
tion of pellagra. Chief among these was Thouvenel. He believed 
that the numerous irrigation canals and the rivers of the Lombardy 
plains considerably increased the evaporization. He thought that 
the air of the near-by Alps was dry and bracing but that at the 
foot hills of these mountains where these two different atmospheres 
met there was produced a condition which favored the development 
of the malady and thereby he accounted for the prevalence of the 
disease in what has been often referred to in the preceding chapter 
as the sub-Alpine country. There were many objections to this 
view. 

Ten years after Frapolli Albera resuscitated the theory of inso- 
lation but he met opponents both in Facheris and Strombio. Rous- 
sel said that he referred to the disease as maladie de I 'insolation du 
'printem'ps. Facheris thought that if the disease depended on the 
sun's rays it would be more apt to appear when the rays were hot- 
test and not early in the spring before warm weather. Strombio 
insisted that there must be some internal morbid cause which ren- 
dered the skin more susceptible to the action of the sun. He said 
further that if pellagrins avoid the sun they escape at least a por- 
tion of the skin disturbance, but this does not retard the progress 
of the disease. This view expressed nearly a century and a half 
ago is as accurate according to present-day belief as any that has 
so far been brought forward. I have compared the role of the sun 



54 A TREATISE ON PELLAGRA 

in the production of the erythema to the photographer's sensitive 
plate which is ready to receive? a light inipivs-ion Imt which will 
forever remain a blank without this action of the light. And on 
the other hand I have repeatedly seen an erythema appear on the 
feet of patients in the hospital confined absolutely to bed. It will 
later be brought out that this erythema of the covered portion of the 
body differs from that of the exposed portions in that the well 
defined lines of demarcation between diseased and normal skin are 
lacking. It should be emphasized at this point that the extent of 
the skin lesion is in no sense an index of the severity of the attack. 
I have seen the so-called pellagra universalis or pellagra with a 
skin manifestation covering all or nearly all the skin surface when 
the attack was most trivial and the patient able to remain at work. 
On the other hand I have seen cases of fatal pellagra in those with 
so trivial a skin disturbance that it would actually be overlooked 
by the patient himself. Then, too, if the sun has even a favoring 
influence in determining the position of the skin lesions why is 
the perianal skin and the vulva as well as the skin of the bend of 
the knee so often the locations ? Again it would be obviously unfair 
to overlook the fact that the exposed parts are affected about one 
hundred times to one time of the unexposed. I have seen the skin 
lesion generally distributed over the upper thoracic and back 
regions in a young woman, but it was noteworthy that the portions 
of skin surface beneath the shoulder straps of the chemise were defi- 
nitely outlined by being absolutely unaffected by the erythema. 
Experimenters have been able to produce areas of erythema at will 
by making holes of the desired size and location in the clothing of 
a pellagra patient. 

In 1862 Bouchard expressed the opinion that the influence of the 
sun was purely secondary and that the real underlying cause was 
poor nourishment. Landouzy wished to know if the sun was sup- 
pressed what would become of pellagra. Roussel answered that to 
suppress the sun would not suppress pellagra. The sun he thought 
did not cause it but was an enemy to pellagra. In 1843 Marchand 
thought it of sufficient moment to Avrite that he found the disease 
under the sign of the zodiac, Belier. 



THEORIES OF ETIOLOGY 55 

Roussel thought that there were enough evidences to prove that 
the name mal de misere was a misnomer. This name owed its 
origin to the occurrence of pellagra among the wretched peasantry 
of Italy. Roussel contended that this could not be the sole cause 
because the disease was not confined to this class. This fact has 
been even better demonstrated in the United States than it was in 
France in the time of Roussel's writing. I have had many patients 
suffering with typical pellagra among the best conditioned classes, 
but, of course, this would not answer the argument entirely because 
a patient may suffer from malnutrition in the midst of plenty. 
I might add that I have observed the disease in the well nourished 
as often as in the poorly nourished. The idea of the disease being 
one of malnutrition is due to the fact that the patient usually does 
not consult the physician until the disease is well advanced, or, on 
the other hand, the physician does not at once diagnose the condi- 
tion. There are many good reasons for a delay in the diagnosis 
of pellagra. One of the most important is that the skin lesion re- 
mains only a comparatively short time and may be so slight as to 
attract almost no attention even from the patient. It is never good 
policy to make a diagnosis of pellagra without the presence of the 
skin disturbances unless the history of the skin lesion is very defi- 
nite. It will be later shown that sprue occurs in the southern states 
and pellagra without the skin symptoms cannot be differentiated 
from this disease. From this the reader will see that pellagra is 
well advanced oftentimes before the diagnosis is reached, and by 
that time there is every reason to expect a condition of malnutri- 
tion as much as one would expect the same thing in dysentery. All 
diarrheal diseases are attended with rapid wasting and pellagra is 
not an exception. In my own experience I find that pellagra causes 
malnutrition but is not caused by it any more than furnishing a 
simple predisposition and this is no more emphasized than in 
typhoid or any other like process. Roussel said that the cause was 
not bad air nor bad water but bad nourishment. It cannot yet be 
denied that bad nourishment in the sense of containing something 
toxic is the cause, but I can deny that bad nourishment in the sense 
of insufficient nourishment is a cause. 



56 A TREATISE ON PELLAGRA 

Jacobo Penada thought that the cause was to be found in the 
absence of wine from the dietary. There was abundant contradic- 
tion to this and later it was proven that alcohol was a decidedly 
active predisposing cause. I have had ample occasion to suspect 
that alcohol did play a very definite part in the causation of the 
disease, and were it not for the fact that pellagra is so apparently 
due to a very definite specific cause I would undertake to 
show that the effect of alcohol was very decided. This last men- 
tioned observer also thought that a cause was to be found in 
the use of salty food. Salt in the pellagrous districts of Italy 
was a luxury because it was, as before mentioned, a government 
monopoly and the price placed it beyond the reach of the poor. 
Roussel and later Lombroso emphasized the importance of salt 
in the dietary as a prophylactic, and the latter went so far as 
to say that salt would do as much in the treatment of pellagra as 
arsenic were it not for the fact that it was not well borne by the 
stomach. 

The cause was also sought in bad rye bread, in the use of 
lard pastry, in millet, and even in rice. Zanetti answered all 
these theories by declaring that the real cause was the nourishment, 
which consisted chiefly of maize in Lombardy, where he did his 
w T ork. 

In 1778 Thouvenel brought forth the view that the cause of the 
disease in the valley of the Po was a condition of the atmosphere, 
but the French physicians thought that this condition merely 
affected the maize which was the chief article of diet. It was at- 
tempted to prove that since the use of maize this section had suf- 
fered from pellagra. Thouvenel, 1 who seems to have accepted the 
idea of the effect of atmospheric conditions on the corn, found more 
followers in the large cities and this was especially true of those 
who had studied the question. Many opposed this view from the 
beginning. The most remarkable observer of this period was Fran- 
zago, who for many years was an advocate of the maize theory but 
gave it up until later in life, when he returned to it and spent the 
last days of his life disputing with Marzari about the priority of 

1 Thouvenel, " Traite" du Climat d'ltalie," 1778. Quoted by Roussel. 



THEORIES OF ETIOLOGY 57 

their respective claims. However, Franzago did not consider maize 
unhealthy but merely an insufficient form of nourishment. He 
dared not, therefore, claim that maize was the sole cause because 
he did not observe the same condition in the cities and yet the same 
food was eaten there as in the country. He thought it was associ- 
ated with the consumption of other foods as well. Marzari had 
observed pellagra in Trevesan for twenty years and held to the 
maize theory as one would to a religious belief. He x said that the 
appearance of the disease was preceded by the constant use of maize. 
The long winter preceding the outbreak of the attack when maize 
was oftentimes the only food to be procured by the poor was in his 
opinion the only cause worth considering. Marzari has always been 
considered the father of the maize theory though he was not the 
first to advocate it. It should be remembered that the older ob- 
servers and even his contemporary, Franzago, did not attribute to 
the spoiled or damaged maize the sole cause of pellagra. Marzari 
seemed to have regarded the noxious substance as a toxin of the 
same general character as ergot and to have classified pellagra with 
ergotism. In his writing on this subject he noted that the Turkish 
wheat (maize) was often picked before ripe and allowed to become 
moist or stored in the undried state. The grain was made into 
polenta without salt. The consumers of this food ate only the 
smallest amount of vegetable food such as cabbage. He also em- 
phasized the fact that maize did not contain a sufficient amount of 
gluten. His observations were made in the sub-Alpine region. It 
is the general opinion that Marzari found the noxiousness of the 
corn in this deficiency of gluten, but a more careful perusal of his 
work has caused me to conclude that he also suspected a toxicity 
as mentioned above. All of his contemporaries attacked his posi- 
tion and the Congress of Medical Societies in 1859 approved the 
position of his opponents. Marzari's work resulted in the division 
of the students of pellagra into the " zeists " (from Zea Mays), or 
those of his view that maize was the sole cause, and the " anti- 
zeists," or those who opposed it. It is a notable fact that as late 
as 1874 the Royal Institute of Sciences of Lombardy officially 

1 Marzari, "Essai Medico-Politique," 1810. 



58 A TREATISE ON PELLAGRA 

opposed this teaching of Marzari which had been greatly enlarged 
and developed by Lombroso. 1 

Gnerrischi in his memoirs is said to have given Marzari the first 
idea of the actual toxicity of maize. 

This view of maize being responsible for pellagra soon spread 
from the sub-Alpine country to all parts of Europe where it was 
used as a food. As early as 1S40 Trompio classed those who grew 
it as enemies to agriculture. About this time Bonafous, a writer 
on medical and natural history subjects, claimed thai lie sought 
in vain for pellagra in the Landes, in the south of France, 
and in all the territory where llanieau had described it. His 
inference regarding the etiology was that there must be some 
other cause than the type of agriculture and the kind of food 
eaten. 

Roussel was very emphatic in the statemenl that pellagra ex- 
isted only in those countries where corn is eaten and never attacks 
those who do not eat it. His observations regarding the history of 
maize in Europe are worth referring to at some length, lie con- 
cluded that maize was unknown in Europe up to the end of the six- 
teenth century and never became naturalized or counted of great 
importance. During the sixteenth and first half of the seventeenth 
centuries it did not occupy any place of importance in the countries 
where pellagra occurred. In Spain in the seventeenth century it 
gradually replaced millet, barley, and other grains in those rural 
districts where Mai de la Eosa had been found. Chief among 
these places mentioned was the Asturias, where the disease was first 
described by Casal in 1735. In France he discovered that maize 
was known about the sixteenth century but it did not become an 
important food until the end of the eighteenth century. In Italy 
he said that after much research he was able to determine that 
maize did not play any important role until after the first half of 
the sixteenth century. Toward the end of this century and the first 
half of the seventeenth the disease began to prevail in Lombardy 

1 Lombroso, C, " Die Lehre von der Pellagra," Deutsch. Versuch. von Hans 
Kurelle, Berlin, 1898. See also bibliograph of Lavinder and Babcock's trans- 
lation of " La Pellagra." by A. Marie, p. 393. and the Index Catalogue of the 
Library of the Surgeon, Surgeon-General's Office, Army Medical Museum. 



THEORIES OF ETIOLOGY 59 

and the Venetian provinces, from which regions it penetrated to 
the Italian Tyrol. About the middle of the eighteenth century 
maize produced a sort of revolution in foods among the people of 
many districts, and during the second half of the eighteenth cen- 
tury this very general use of maize in place of the other cereals 
extended almost to the northern confines of the peninsula. It has 
been shown that the general extension of pellagra was first noted 
about the time of this popularity of maize in Lombardy and in 
Venetia several years later. The actual date of the general inva- 
sion of Lombardy was 1771. In 1845 Balardini wrote a work on 
the condition in upper Italy and his views and experience coincided 
with these of Roussel. The latter writer seems to have carefully 
studied the geographical distribution of both pellagra and the culti- 
vation of maize. He said that he found that pellagra under many 
names extended over large areas in the temperate climate of Europe 
between 42° and 46° C. and always reached to the very limits of 
the area planted in the " American cereal." To the north of this 
zone Roussel said that he could show that the disease did not occur. 
In the middle of this zone extending to the warmer climate where 
maize culture is more perfected and the grain is allowed to become 
perfectly ripe before harvested, pellagra became gradually rarer as 
conditions gradually improved until finally it was not found at 
all in those districts where maize reached the highest degree of 
perfection. This report of Roussel would appear at first thought 
conclusive, but a further study of the case weakens his contention. 
Probably no student has ever so thoroughly combated this state- 
ment as Sambon. 1 Among his many excellent examples of error he 
mentions that Conti, Chief Medical Officer of Ravenna, stated that 
pellagra was not confined to the small mountainous region in which 
maize was eaten, but that it occurred also in the district of Lugo 
where maize is not used. To prove the correctness of this diagno- 
sis he suggested that a new examination be made using Gosio's 
methods, not excluding the test with specific precipitines. Sam- 
bon 1 states emphatically that the topographical distribution of pel- 
lagra does not coincide either with the distribution of maize culti- 

1 Sambon, L. W., Progress Report, 1910. 



60 A TREATISE ON PELLAGRA 

vation or with that of maize consumption. There is much that 
might be said on both sides of this question. Sandwith, 1 after find- 
ing pellagra in Egypt, attempted to determine if it also occurred 
in the United States, the real home of the grain, but his inquiries 
were all replied to in the negative. At this time this was inter- 
preted by some as a proof that maize could not produce the disease. 
It should be remembered in this connection, however, that this 
grain is at home in this country and does not reach the same state 
of perfect development in any other land. Again, it has been 
shown that there is a probability that pellagra has existed here 
for many years. The patients who have been under my care almosl 
invariably give a history of eating maize in some form for the 
reason that any one in the south who does not eat corn bread, 
hominy, or some other of the many delicious southern dishes made 
from maize, is counted a very peculiar person. These people who 
give this history of maize consumption never eat it exclusively as 
do the Italian peasantry but they can never deny the fact that they 
do eat some daily. It has been exceptional to find a patient who 
ate maize exclusively. In those afflicted I have made ir a rule to 
absolutely exclude corn from the diet for all time thereafter, but it 
has never affected the recurrence of the erythema in the next spring. 
On the other hand I have seen patients who refused to give up the 
com bread and the erythema was apparently not affected by this 
persistence. I have seen recoveries in those who did not refrain 
from the use of maize. Neither of these facts furnishes any con- 
clusive evidence ; they are merely suggestive. 

According to Roussel there was not a country affected by pel- 
lagra which did not also suffer from poor maize cultivation. He 
illustrated one of his points by the report of Zantedeschi to Balar- 
dini, in which the fact was brought out that pellagra cases occurred 
in large numbers from 1S04 up to 1S16 when it disappeared, due 
to the fact that the high prices of maize forced the poorer classes 
to use potatoes and vegetables in place of it. In 1819 there was a 
decided fall in the price of maize and pellagra reappeared and has 
persisted from this date. Because flema salada occurred in a sec- 

1 Sandwith, J., Trans. Nat. Pell. Conference, 1910. 



THEORIES OF ETIOLOGY 61 

tion where there was no corn to explain the cause, Roussel thought 
to disprove its identity with pellagra. As mentioned above, the 
same thing was done regarding the question of the condition known 
as pseudo-pellagra of Billod. As before mentioned, if this pseudo- 
pellagra is not pellagra, then the disease in the southern states 
which has caused such consternation is not pellagra, for the de- 
scription of this false pellagra of Billod is absolutely the same 
clinical entity as our pellagra, and I might go a step farther and 
say the same for the descriptions of the Italian and French disease. 
One can hardly fail to sympathize with Sir Patrick Manson's rather 
contemptuous remarks about true pellagra in a consumer of maize 
and false pellagra in one who did not eat this much-abused Ameri- 
can cereal. 

There soon grew up among the zeists two schools or, more cor- 
rectly, two subdivisions of this school. One thought that maize was 
an insufficient food and the disease was one of malnutrition, while 
the other school attributed the cause to a fungoid growth on the 
maize. This growth was known as verderame or verdet and was 
thought to be due to the action of the sporisorium maidis. This 
was the opinion of Balardini, but it was through Costallat that this 
doctrine was advanced in 1857. He considered pellagra a slow 
form of poisoning due to this verdet. This parasite was first found 
in the markets of Bagneres-de-Bigorre. Experimental demonstra- 
tions were made by Balardini, Ellia, and others using maize con- 
taining the verdet or polenta made from it. Chickens were fed on 
it and manifested a number of symptoms which were thought to 
resemble pellagra. At first there was loss of appetite followed by 
loss of weight, droopiness, tremulousness, and great thirst. At 
the end of twenty-eight days the last stage is reached in exhaustion, 
soon followed by death. Ellia demonstrated that there was 
roughening of the skin and a furfuraceous desquamation. Lussana 
and Erua injected into the veins of dogs and birds meal made 
from maize which contained verdet. In one experiment the aqueous 
extract was used, in another the powder itself of this damaged 
grain. The resulting symptoms were dyspepsia, coagulation of the 
blood, pulmonary ecchymoses, vomiting, congestion of the liver, and 



62 A TREATISE ON PELLAGRA 

intestinal inflammation which were attributed to the severity of 
the experiment, but such was not thought to be sufficient to explain 
the " apathy, clonic convulsions, and paralysis, more or less com- 
plete, especially of the hind legs, which are observed in the dogs 
that, for a time, survive the initial intravenous injections. These 
phenomena show characteristics too marked to be misinterpreted." i 

It was through this work of Balardini that the idea of the so- 
called " zeitoxic " school headed by Lombroso had its origin. 

The view that the cause consisted in the insufficiency of the nutri- 
tive property of maize was not abandoned without a struggle. The 
advocates of this theory thought that through its deficiency in 
nutritive elements there was an interference in the neuro-muscular 
repair following insufficient protein alimentation. This theory 
differed little from the idea of Marzari in the insufficiency of the 
gluten in maize. 

The question of the insufficiency of maize as a food may be dis- 
missed with a word. All the recent investigation of its food value has 
shown conclusively that it is second to none in this respect. Snow 
of the United States Department of Agriculture (Report 49) say- : 

" The growing of maize is not only the most important branch 
of our arable agriculture, but it forms the foundation upon 
which rests a large part of our wonderful rural development. 
About 96 per cent of our crop is annually consumed in this coun- 
try, and more than 80 per cent never crosses the lines of the county 
in which it is grown. It is the great American crop. On the farm 
it feeds the working animals, fattens the beeves and hogs, is an 
important constituent in butter and cheese production, and forms 
part of the family ration. It appears on the table in American 
homes both as meat and bread, and again in the form of tempting 
and appetizing delicacies skillfully prepared from some of its 
many products. . . . Its value as part of the soldier's ration is 
appreciated in this country, where the ration established by the 
military authorities include for bread ' 18 ounces of soft bread or 

1 Marie, A., " La Pellagra." Translation by Lavinder and Babcock, also in 

RoussePs work. 



THEORIES OF ETIOLOGY 63 

flour, 16 ounces of hard bread, or 1 pound and 4 ounces of corn 
meal.' The value of corn meal as a constituent of the army ration 
was demonstrated practically during the War of the Rebellion. 
The larger portion of the bread used by the southern armies was 
from corn meal, while at the same time it furnished a large part 
of the food supply of the Federal forces. Its value here received 
the most crucial test which could be applied possibly, and the 
wonderful strength and endurance shown by the combatants on 
both sides is sufficient evidence of its value." 

The earlier literature on the maize theory of the etiology of 
pellagra is so voluminous and there is so much of experimental 
work to be considered in connection with the experimentation of 
Lombroso and his followers, that it is not possible to deal further 
with the development of this maize theory though its interest and 
importance are fully recognized. The history of the development 
of this idea is a good account of the development of modern 
laboratory technique. 

Cesare Lombroso was born of a Jewish family in 1836 and died 
suddenly in 1909, after spending the last twenty-five years of his 
life in the study of the etiology of pellagra. His work on pellagra 
was begun in 1872. One of his biographers * has charged him with 
an exaggerated tendency to refer all of the mental facts in his work 
as a psychiatrist to biological causes, and also a serious want of 
accuracy and discrimination in handling evidence. In spite of this 
his work marked an epoch in the study and management of crimi- 
nology. There are many who have the same criticism of his pel- 
lagra work as that mentioned of his psychiatric work. But in 
any event the fact should not be lost sight of that he gave of his 
time and wonderful experience in mental diseases for the amelio- 
ration of one of the greatest scourges of modem times, from which 
his country suffered more than any other. Time may prove that 
there were many errors in his conclusions, but in spite of any sub- 
sequent developments the name of Lombroso will ever be inter- 
woven with pellagra. 

1 Encyclopedia Britannica, Edition of 1911. 



64 



A TREATISE ON PELLAGRA 




The study of spoilt corn has occupied the attention of many 
since the beginning of Lombroso's work though it should be renn in- 
hered that in the time of Hameau there were chemical studies done 
with the same idea in mind. 

Corn J has been repeatedly shown to be very subject to various 
deteriorations because of the large amount of fat contained in the 
embryo and also because the embryo is so poorly protected from 
accidents, lying as it does on the surface of the kernel hardly cov- 
ered at all. The mass of perisperm which lies around the embryo 
is often changed into a kind of detritus and in its place there is 
a cavity in which may be found a coleoptera or mite which has been 
suspected as the indirect cause of the disease by making a place of 
refuge for the disease organism whatever it may be. When the 
kernel is diseased there is atrophy of the embryo which does not 
fill out the usual space between the perisperm and the hull of the 
caryopsis. This unoccupied space again is supposed to be a source 
of danger by making an excellent site for the growth and develop- 
ment of fungoid organisms. On gross examination spoilt corn is 
distinguished by its cracked or wrinkled hull, its tawny gold color, 
by an absence of luster, and by an enlargement of the embryo which 
assumes a dark color. There often occur on the exterior of the 
kernel brown spots or green areas which suggest verdigris and 
which strongly contrast with the normal white color which the 
grain should have. Sometimes the grain has the ordinary appear- 
ance, but closer examination reveals eroded spots scattered over the 
surface of the kernel which again favor the entrance of moulds. 
The growth of this mould produces a green powder which is some- 
times confused with the aearus faring, but the latter can be easily 
distinguished by its movement. The meal of spoilt corn is readily 
detected by its tawny yellow color. Sometimes this color is a gray- 



1 This portion of the chapter is gleaned with slight change of original text 
from the translation of " La Pellagra," by A. Marie. This translation was 
made by Lavinder and Babcock in 1910. Marie's work was a synopsis of the 
Italian work of Lombroso but to be absolutely accurate the translators have 
compared their translated work with the original text of Lombroso. Acknowl- 
edgment is hereby made to the translators for their good work and for my in- 
debtedness to them. E. J. W. 



THEORIES OF ETIOLOGY 65 

ish brown. There is an aromatic odor and a bitter taste. It is 
said that good meal when rubbed in the hands gives the odor of 
polenta, but if bad the odor is mouldy. This would hardly com- 
mend itself as a reliable test of so important a matter. It is further 
recognized that these peculiarities would occur only in the event 
of advanced deterioration. 

When the kernels of spoilt maize are digested in 90 per cent 
alcohol the grayish yellow color becomes an intense red and the 
alcoholic solution takes on the same red color which deepens with 
time. Such change does not take place if the grain is sound, and 
after several months the only change is a slight lemon yellow color 
of the alcohol. The red color was not found by Babes and Sion in 
Eoumania and was not observed by Marie except in artificially 
spoilt maize. 

When maize is treated with a dilute solution of caustic potash, 
if deteriorated, the hulls become reddish brown and later the solu- 
tion becomes brown and has a very characteristic odor. The color 
is said to change more rapidly if the degree of spoiling is great. 
When this alkaline solution is neutralized with tartaric acid, flakes 
resembling coffee in color are precipitated which have the odor of 
spoilt corn. This precipitate is insoluble in water and ether but 
soluble in alcohol. 

Lombroso found that the tincture of spoiled corn contained three 
substances. The first was a ruby red liquid which had a strong, 
bitter taste and the odor of spoilt maize. This substance was 
soluble in ether and alcohol, but insoluble in water. It became 
resinous when exposed and did not yield a precipitate with the 
iodide of potassium. This tincture contained the oily portion of 
corn. It was colored by a red substance which can be isolated 
from the ethereal solution by potassium hydroxide. W T ith this 
latter substance and benzine it yielded a bright yellow precipi- 
tate and a drop of it on paper made a grease spot. This was des- 
ignated the red oil of bad maize and will be referred to by that 
name. 

The second substance was called by Lombroso pellagrosein and 
was the toxic substance about which much will be said later. This 



66 A TREATISE ON PELLAGRA 

substance was reddish brown. It was styptic and very bitter. It 
was soluble in ordinary alcohol but a yellow precipitate was pro- 
duced by absolute alcohol which was dissolved by adding a small 
amount of distilled water. A yellow flaky precipitate was pro- 
duced by the chloride of platinum. Sulphate of copper produced 
a green color and at the end of a certain time a reduction of pro- 
toxide took place. It was soluble in acetic acid and a solution of 
potassium hydroxide, and was precipitated by sulphuric acid. 
When it was treated with water it separated into two parts. One 
of these, which was soluble, was precipitated in the form of a 
brown amorphous powder. The other was soluble, producing a 
bright yellow solution. This latter was the pellagrosein. 

The third product was the resinous substance of diseased maize. 
This substance when heated with ether was solidified, and on ex- 
posure to the air became quite hard. It was soluble in caustic 
potash and in dilute alcohol. It was insoluble in water, benzine, 
and absolute alcohol. Heated it became semi-solid and could be 
drawn out in strands like sealing wax. It burned with a white 
flame, and the odor was said to resemble that of burnt polenta. 

The tincture of sound corn produced three substances. The 
first was not red but amber. It was soluble in ether and did not 
have the strong odor of the red oil of spoilt maize. It had all the 
properties of the oil of corn and none of the diseased product re- 
ferred to above. The second was also yellow. It did not form 
a precipitate with iodide of potash nor with absolute alcohol. 
Caustic potash and sulphuric acid produced a precipitate soluble 
in ether. It resembled the resinous substance of spoilt maize. 
Substances isolated from damaged maize, according to Marie, were 
chemically analogous to those isolated from spurred rye. and if 
these toxic substances from maize were given over a long period 
in small doses the results were the same as those of ergot given 
in the same manner. The chemist, Erba, who worked with Lom- 
broso, perfected the method of extracting the various chemical 
substances above mentioned. In casks filled one third full of 
water he added a large amount of sound corn. This was shaken 
daily and examinations made. The grain passed slowly through 



THEORIES OF ETIOLOGY 67 

acetic, alcoholic, lactic, and putrid fermentation. It was then 
dried. The kernels preserved their usual form but took on a dirty 
yellow color, while the embryos were intensely yellow and con- 
tained more oil than usual. This grain was found to be easily 
pulverized. There was an abundant growth of a number of moulds 
including the aspergillus, the eurotium herbariorum, and the 
odium lactis. 

The maize was then dried until it had decreased in weight 24 
per cent. After grinding, the meal was treated with 40 per cent 
alcohol to extract the soluble substances. This tincture was dis- 
tilled on the water bath and the residue contained an oily sub- 
stance called oleoresin of spoiled corn which was analogous to the 
red oil, a substance which was identical with the alcoholic extract 
or pellagrosein, a resinoid substance called the glutinous substance 
of spoilt maize, and finally an aqueous extract. • 

It was shown that corn bread moulded and allowed to spoil up 
to lactic fermentation contained a considerable amount of fat 
which remained solid at 19° C. Sound corn did not yield as large 
an amount of this oil. Brugnatelli analyzed the oil and the alco- 
holic extract of spoilt maize and found a bitter, nitrogenous sub- 
stance which gave the reaction of an alkaloid resembling strych- 
nine. It was a notable fact that this alkaloid was not found in 
sound corn. 

Penicillium glaucum is found in all spoilt grain according to 
Marie. 1 It forms the greenish-blue dust which is found on most 
of the kernels of damaged maize. It does not remain on the sur- 
face but penetrates into the interior when corn is placed on the 
ground in winter or while fermenting in damp granaries. 

The best known parasite of bad maize is the sporisorium maidis. 
It has a green color and is found in the furrows of the embryo. 
Under the microscope it resembles little globules united by fine 
filaments but easily separated by rubbing. It is a hypomycete. 
Balardini and Cesati were the first to describe it. They were able 
to produce in man by its use gastritis and diarrhea. In chickens 

1 Marie, A., " La Pellagra," 1909, and Lavinder and Babcock's translation 
of the same, 1910. 



68 A TREATISE ON PELLAGRA 

it caused loss of feathers, decided loss of weight, and droopiness. 
It was supposed to have no important connection with pellagra 
because Lombroso was able to find only three specimens in Lom- 
bardy during many years. The large number of moulds mentioned 
by Marie are not of sufficient interest or importance to justify 
mentioning at this time. 

The bacteriology of damaged maize has been carefully studied 
but the results have been by no means uniform. The commonest 
of these is the bacterium maidis which is morphologically identical 
with the bacillus mesentericus vulgaris. It is a small cylindrical 
bacillus which is very motile, growing in chains of two or three 
organisms. It stains very readily in nearly all the usual laboratory 
stains, but especially in an alcoholic solution of methyl violet and 
the usual aniline dyes. It is said to resist a temperature of 90° C. 
and grows luxuriantly at from 25 to 30° C. This organism is 
found in many specimens of meal and often in pure culture. 
Marie said that this organism, which cannot be distinguished from 
the potato bacillus, was found in large numbers in freshly baked 
bread. When this bread was placed in a damp chamber, at the 
end of ten days it showed numerous yellow and blue colonies which 
were found to be composed of a large variety of organisms of too 
little importance in the work before us to justify enumerating. 
The only one of these organisms of any importance seems to be 
the bacillus maidis, which has been found in sound meal. In 1881 
Majjochi found a very motile bacillus in sound corn as well as 
in the diseased, though in the latter it was always much more 
abundant. He reported that he thought that it was this same 
organism which he found in the blood of seven pellagrins early in 
the disease. Cuboni found it constantly on spoilt maize and he 
recognized its marked similarity to the bacterium thermo, though 
it resisted a higher temperature. Marie constantly referred to 
the bacteriology of corn shipped by water and the various effects 
of sea water on the growth and distribution of the various organ- 
isms in the kernel. All of this will be passed over in this work 
because it can have no bearing on the situation in the United 
States as all maize in this country is shipped by rail. Cuboni 



THEORIES OF ETIOLOGY 69 

said that the bacterium maidis occurred in damp corn and espe- 
cially if the corn was immature, and that dryness arrested the 
development but did not destroy it, hence corn well dried can later 
become spoilt by this organism in the presence of moisture. This 
organism resists a temperature of 100° C, hence it would not be 
impossible to recover from polenta the living bacillus. Its growth 
on gelatine causes liquefaction and in the test tube the growth 
assumes a funnel shape. Coboni's work on the feces of pellagrins 
and healthy individuals showed that in both classes the organism 
was present but that in the pellagrin the number was larger. He 
said that when taken into the intestinal tract in spoilt polenta the 
organism multiplied very rapidly and caused a true intestinal 
mycosis. 

Peltauf and Heider studied the same bacillus and identified 
it with the potato bacillus. They found it to be the inhabitant of 
the intestinal tract of fifteen pellagrins, but its presence there was 
not regarded as pathologic. The bacillus was an aerobe, it was 
motile, and it produced spores at one end or in the middle. I have 
done a great deal of work with this organism and am convinced 
that it is harmless and in no way connected with pellagra as a 
causative factor. 

Heider in Ludwig's laboratory studied the chemical products 
of the life of the bacterium maidis and concluded that at a high 
temperature this organism could, in the presence of moisture, bring 
about changes in corn. Recent experimentation demonstrates that 
in polenta it resists the temperature counted sufficient for thor- 
ough sterilization, but after repeated sterilizations under high tem- 
perature it is destroyed. Grown in the incubator on polenta after 
three days it produces a strong odor of mice. Marie concluded 
that its action was indirect, acting as did the oidium lactis in 
producing a toxic substance from the parenchyma of the grain. 
Peltauf's animal experimentation by the subcutaneous injection 
in rabbits, guinea pigs, and rats was entirely negative except in so 
far as it was proven that the organism was not pathogenic. But 
when he infected the alcoholic extract of corn meal with this or- 
ganism and allowed it to stand for three months, he was able to 



70 A TREATISE ON PELLAGRA 

produce coma, paralysis, and death by the injection of the product. 
Cultures of the potato bacillus in polenta produced the same re- 
sults which proved the identity. Heider and Gorizia removed 
from spoilt maize a substance giving the reaction of an alkaloid 
which killed rats after producing anesthesia and narcosis. 

These experiments were repeated on a larger scale by Lom- 
broso and others with the following results. 1 

" If cultures on polenta of one, two, six, and up to seven days 
old, are given to animals they become accustomed to it slowly; 
the initial diarrhea, which is the only symptom, may even cease; 
the cultures over four or five days old are refused, perhaps because 
of their bad and very pronounced taste. 

" As a consequence of this nourishment, digestive troubles are 
produced, sometimes vomiting, almost always diarrhea, but never 
derangement of the sensibility or of the motor system. At the 
end of some days the weight begins to diminish, but then main- 
tains itself within normal limits. The temperature is usually 
maintained at normal; in the first days only two cases showed a 
slight evening rise. 

" The attempt to cultivate this bacillus on wheat bread met with 
little success ; two dogs fed for fourteen days with this bread 
showed no change. 

" An experiment was then made with the alcoholic extract ob- 
tained from a culture on polenta twenty-five days old. The extract, 
prepared by Professor Fileti, was injected into three dogs under 
the skin of the back in doses of 5 per cent, 10 per cent, and 25 
per cent of the weight of the animal. The two dogs which had 
received the largest doses died two days later, after presenting the 
following symptoms: 

" Paresis of the hind legs, almost continual tremor, general 
depression, which was rapid and progressive, gradual loss of vol- 
untary motion, complete paralysis of the hind legs, mydriasis, 
slight increase of temperature, acceleration of respiration and 
pulse, insensibility, bloody diarrhea, and death with prolonged 

1 From Lavinder and Babcock's translation of Marie's " La Pellagra," which 
was a synopsis of Lombroso's work. 



THEORIES OF ETIOLOGY 71 

agonistic state. At the autopsy, edema of a hemorrhagic nature 
in the hypogastric region, extravasations in the spleen. 

" The dog inoculated in the proportion of 5 per cent of its 
weight exhibited at the beginning the same symptoms, but at the 
end of the second day his condition improved ; however, the hind 
legs remained paralyzed and the diarrhea continued for several 
weeks with a remarkable diminution of weight. 

" In the case of two other dogs, intravenous injection in the 
proportion of 5 per cent of body weight caused death after the 
development of the above-mentioned symptoms. 

" Injections into ten frogs, with corresponding doses brought 
on death in three hours with paralysis, diffuse ecchymoses on the 
interior of the thighs and in the hypogastric region. Intravenous 
injections of the extract of sound polenta up to 10 per cent had no 
evil consequences ; the same may be said of the subcutaneous in- 
jections made in double doses." 

The final conclusion of Lombroso was that pellagra was an in- 
toxication disease which was produced by the action of certain 
organisms on maize. These organisms in themselves were harm- 
less but possessed the property of producing a poisonous ptomaine 
when they came in contact with the kernel of the maize. From 
the above-mentioned experiments it is plainly seen that the bacil- 
lus maidis cannot be counted pathogenic. It is not so harmful 
even as the bacillus coli communis, which when placed beyond its 
normal territory in the animal economy becomes at once patho- 
genic. !Not so much can be said of the bacillus maidis because it 
can do no direct harm. It is accused of being one of the pto- 
maine producers, but opinion is not altogether united on this mat- 
ter. Lombroso and Peschel thought it was active in the decompo- 
sition of albuminoids and hydrocarbons and that it might possibly 
be counted an intestinal irritant. It is important to consider that 
this bacillus is found in the best grade of sound maize and in the 
normal intestinal tract in which latter place it is known as the 
bacillus mesentericus vulgaris. Efforts have been made to recover 
it from the blood of pellagrins but it cannot be done. For two years 



72 A TREATISE ON PELLAGRA 

I made routine blood examinations of every case of pellagra which 
I saw and in all stages, but the bouillon invariably remained 
sterile. Cuboni made thirty attempts in cases of pellagra and 
his results were also negative. The same negative results occurred 
in the skin lesions and intestinal tract of dogs supposed to have 
the disease, while animals fed on the tincture of spoilt corn with 
all organisms removed were supposed to develop symptoms of 
pellagra. It is not my opinion that this condition was pellagra 
because I have never been satisfied that the disease can be experi- 
mentally produced even in the presence of such testimony as that 
of Lombroso and Marie above recorded. Lombroso always em- 
phasized the fact that in order to produce pellagra it was neces- 
sary to feed the animal for some time on the toxic products of 
deteriorated maize. This idea owed its origin to the fact that 
spurred rye does not cause ergotism from one or two exposures 
but by a constant repetition of the poison. Tuczek, 1 who made 
a careful study of a series of cases of pellagra and ergotism, 
thought that the two diseases belonged to one class, grain intoxi- 
cation. There are many objections to the classification of pella- 
gra with ergotism but the one which is most logical is the patho- 
logic basis. Even Marie is forced to acknowledge that the pathol- 
ogy is not of such a character as ergotism but points to a parasitic 
cause. Sanibon's work on this phase of our study is most impor- 
tant and will be referred to at length later. It is reasonable to 
classify this disease on a pathologic basis because the etiology is 
in doubt, and if such a classification is made it will place pellagra 
in that group of diseases with trypanosomiasis, kala-azar, and 
Rocky Mountain fever. This pathologic condition is a roimd cell 
perivascular infiltration of the tissues. In addition to this there 
is an increase of the mononuclear elements of the blood which 
is equally characteristic of a disease caused by an animal 
parasite. 

In a large number of cases it has been my rule to enter on the 
case record the character of the food eaten and I have been struck 
by the fact that usually the reply is that the patient did not eat 

1 Tuczek, ¥., " Klin. u. Anat. Sturlien ueber die Pellagra," 1893. 



THEORIES OF ETIOLOGY 73 

much corn food, and then it was usually hominy or grits which is 
not so apt to become deteriorated nor is it eaten half raw as is so 
often the case of corn bread. I have had patients with pellagra 
who had never eaten any corn food at all. One of my fatal cases 
said that when he was seven years old his father told him that if 
he would eat one piece of corn bread he would be rewarded by a 
visit to Robinson's circus. This was the only time in his life that 
he ever ate maize in any form, but even the most ardent zeist could 
not deny the fact of the case being one of pellagra. In meeting 
this argument a zeist confrere, who had acknowledged the correct- 
ness of the diagnosis, suggested that the wheat flour might have 
been adulterated with corn meal, so I investigated this possibility 
with the result that I found that he ate flour from his own mill 
and that he knew that there was no adulteration. This same zeist 
thought he had solved the problem in the discovery that the patient 
drank corn whisky for which North Carolina is more or less fa- 
mous. On investigating this point it was learned that the patient 
did not drink corn whisky until after he became a victim of pel- 
lagra. In this connection it might be well to say that alcohol is 
a decided predisposing cause of pellagra and in my series it was 
the rule for male patients to be alcoholic. 

It is exceedingly difficult to argue this maize theory of pellagra 
in the southern states with any fairness to the anti-zeist side of the 
question for the reason that a native-born Southerner seldom goes 
through the day without eating maize in some form. It largely 
holds the place in this particular section which is held in other 
sections by wheat. Every southern home has boiled hominy or 
grits for breakfast with the same regularity that the Scot has oat- 
meal. In addition to this unvarying dish there is often added corn 
meal muffins for the breakfast bread. For the mid-day meal, corn 
bread is a common dish, and for the evening meal it is exceptional 
for some dish made of maize to be omitted. So it is readily seen 
that there is small chance for a Southerner to escape maize in 
some form, and as a general proposition it may be said that all 
the inhabitants of the southern states eat maize in some form at 
least once daily. This makes it impossible for any one to say 



74 A TREATISE ON PELLAGRA 

absolutely that corn meal could not have played some part in the 
causation. 

Marie argues that in no parasitic disease is there the same 
amelioration after change of food as in pellagra. In reply to this 
I can say with as much positiveness that the same wonderful 
change is often brought about in my patients without any change 
of food at all and by the use of arsenic in the form of atoxyl. I 
have in my mind a young woman who has gained thirteen pounds 
in the past six weeks by the atoxyl treatment without any other 
change in her manner of living. I have seen a laborer recover 
without changing his food, place of abode, occupation, or anything 
else that could have any bearing on the disease. On the other 
hand, I have seen relapses in patients who had apparently re- 
covered and who had not eaten maize in two years. It is impor- 
tant to know in considering this question that the rich and the 
poor alike in the southern states buy the same quality of corn meal 
from the same barrel and are subject, therefore, according to the 
terms of the corn theory, to the same condition. Pellagra has 
appeared in sections of North Carolina where the maize has been 
raised by the people for a century or more in the same manner 
as now employed and ground in the- same old-fashioned water 
mills. In such localities I have been unable to discover any 
change in the manner of living during the past half century, espe- 
cially in those settlements far removed from the railroads. How 
can maize play a part in the causation of the scourge which in 
some instances has taken off a considerable percentage of the whole 
population ? "Why should the same thing not have occurred long- 
ago if the maize was at fault ? Such questions cannot be answered 
by the zeists. For the sake of argument suppose it is granted that 
these people have only recently begun the use of corn meal from 
the great corn states of the West and that the disease has entered 
in this way. It is a notable fact that the maize grown in the "West 
is far superior to that grown in the South, and at first glance it will 
be seen that the dryness of the W T est would be more favorable for 
keeping this grain in a perfect state than in the South where the 
humidity is greater. It is true that bad corn is often received in 



THEORIES OF ETIOLOGY 75 

the South from the West, but there is no one thing in which the 
American merchant is so proficient as in detecting such corn and 
in claiming indemnity from the railroad companies which are re- 
sponsible for the delivery in good condition. Some might argue 
that this corn is never destroyed. That is true, but it is equally 
true that it is never eaten by man. It is usually sold as chicken 
food that has been known to kill fowl and cattle, but I have 
never seen any similarity between this acute grain poisoning and 
pellagra. 

Marie said that in 1883 the maize crop of Mazze and of Vischi 
was destroyed by inundation and by hail. Some of the grain was 
bought and examined by Gibelli and Mattirolo who found the as- 
pergillus, the rhizopus, mites, and the bacillus maidis. This dam- 
aged grain with other food as milk, meat, and wheat bread was fed 
to dogs and chickens. In spite of the mixed feeding there was a 
loss of weight in the dogs which began from three to twelve days 
after the commencement of the use of the maize. There was also 
a rise of temperature coincident with the loss of weight which was 
attributed to a toxic pyrogenetic substance contained in the grain. 
There was some reduction in the red blood cells but this anemia 
was not constant. It was shown by this that nourishment with 
spoilt maize does not cause chronic inanition because in such a 
state there is a constant decrease of red blood cells. Two of the 
dogs showed an increase of red blood cells. 

There was frequently present tonic muscular spasm and in- 
crease of the tendon reflexes. In two dogs the tetanic condition 
was very marked. The inconstancy of this phenomenon was ad- 
mitted. In seven out of ten there was a pronounced torpor of the 
muscles ; in six, a cerebral torpor ; in three, loss of sensibility ; in 
four, muscular tremor. 

Diarrhea was said to be more pronounced than in man and was 
often preceded by refusal of food and dysphagia. 

The erythema was observed in only one case. This dog remained 
free from anemia, torpor, and spasmodic phenomena, and it was 
noted that the sitophobia and paresis disappeared with the appear- 
ance of the erythema. 



76 A TREATISE ON PELLAGRA 

Marie's x conclusions are given thus : 

" To sum up, we can say that in dogs pellagra shows itself some- 
times under the anemic form, sometimes under the spasmodic 
form, and sometimes under the cerebral form, which is precisely 
analogous to the pathologic anatomy and symptomatology of pel- 
lagra in man, in whom it is erroneous to speak of pellagra in 
general and is more didactic than scientific to make divisions into 
first and second stages. A more accurate division would be into 
anemic, spastic, tabetic, cerebral, and other similar forms of 
pellagra. 

" Nutrition with bread from moulded corn calls forth the same 
symptoms as nutrition with the grain or meal of moulded corn. 
If it never causes true tetanic phenomena, it is, however, accom- 
panied by rigidity of the lower extremities, with exaggeration of 
the tendon reflexes — symptoms more characteristic of pellagra. 
Later, cutaneous erythema, the most typical symptom of pellagra, 
shows itself distinctly. This was lacking in other experimental 
animals, although it is known to occur in ' enmaizados ' horses in 
Mexico, in which it is notable that stupidity and dysphagia appear 
shortly before the erythema, and disappear with its advent. And 
this is in wonderful accord with the observations of medical prac- 
tice which tend to establish an antagonism between the nervous 
phenomena and the skin symptoms. Perhaps localized hyperemia 
acts as a cutaneous revulsion — one sees nervous diseases modified 
by the employment of a strong irritation of the skin. In gen- 
eral the symptoms are more benign in animals fed on mouldy 
bread. 

" In twelve chickens fed on spoilt corn convulsive phenomena 
were exceptionally noted, and if a complete marasmus could be 
excluded, the spoilt grain alone produced increase of weight, but 
finally death intervened after atrophy of the feather follicles, with 
changes in the skin and horny appendages. A fact worthy of re- 
mark is that chickens entirely tame for months became very wild 
at the end of five or six months on the regimen of corn; they 

1 Lavinder and Babcock's translation of Marie's " La Pellagra." 



THEORIES OF ETIOLOGY 77 

fought their companions and had to be shut up. Another chicken 
had photophobia and was unwilling to leave the cage. 

" Taken all together, the disease was less pronounced in the 
chickens than in the dogs; however, the chief effects of nourish- 
ment with spoilt corn, especially the cutaneous symptoms and mus- 
cular disorders, showed results analogous to those of the subcuta- 
neous injections of extracts of oil and of other preparations of 
spoilt corn. 

" The proof seems, then, to be regarded as established, that in 
pellagra the chronic poisoning does not come from microbes in- 
fecting the animal organism, but from the chemical transforma- 
tions of the parenchyma of corn ; and since the more important 
toxic substances pass into the tincture made from the grain, it 
would seem wise and profitable to study experimentally the action 
of this tincture. This would seem all the better since the tincture 
is very well adapted for administration to human beings." 

The fact has not been established from these experiments that 
pellagra was the condition produced. It is acknowledged that in 
only one dog was there an erythema. In man we do not dare to 
diagnose pellagra without the skin manifestations, hence it does 
not seem reasonable to expect the diagnosis to be accepted in the 
lower animals without the characteristic skin manifestations. 
There are many other conditions which could be equally well 
attributed as the cause. As said before, it has never been proven 
that any of the lower animals are susceptible to pellagra. 

Lombroso and Dupre found that the glutinous and resinous 
substances from maize produced no effect in man or the lower 
animals. The toxic substance which was pellagrosein when given 
to dogs produced droopiness and diarrhea and in man it caused 
torpor, anorexia, and nausea accompanied by diarrhea. It was 
said that with care a toxic action on the lower animals could 
be produced by pellagrosein. 

The following experiments were made by Lombroso 1 and 
counted by him conclusive evidence of the correctness of his 
claim. 

1 Lavinder and Babcock's translation of Marie's " La Pellagra." 



78 A TREATISE ON PELLAGRA 

" In frogs clonic convulsions appeared half an hour after the 
injection of pellagrosein in a strong dose of 50 centigrams. At 
the end of an hour there were increased motor reflexes and sensi- 
ble diminution in the cardiac pulsations. Two hours later the 
movements of the heart gradually diminished and a tetanic state 
supervened which increased till death. In other experiments it 
was noted that at the end of a quarter hour the frog took a vertical 
position in the water. If placed on its back it did not turn over, 
and displayed fibrillary contractions of the lower limbs; at the 
end of a half hour complete narcosis appeared ; after three-quar- 
ters of an hour anesthesia to the strongest stimuli ; one hour later 
tonic convulsions, very much increased reflex excitability, and a 
pronounced tetanic state; three hours later death. A very small 
frog after an injection of 5 centigrams died immediately. 

" In a great number of experiments there was found very 
notable differences in results, such differences being dependent 
upon the size of the dose and the time when the substance used 
had been prepared, whether in August or in September. 

" With small doses a tetanic state appeared in 90 per cent of 
the cases, especially if the frogs had been placed in lukewarm 
water. Sometimes this state was preceded by paresis, or perhaps 
death followed it in half an hour to twenty-five hours. 

" In the case of other frogs with doses of 25 to 100 centigrams 
tonic cramps appeared in all the cases and paresis of the ex- 
tremities was produced to such an extent that the animals rested 
vertically in the water. In 27 out of 100 frogs tetanic convulsions 
with narcosis preceded death which occurred usually in thirty 
minutes. In the cold months the substances had scarcely a visible 
effect and even that frequently was evident only on close ex- 
amination. The influence of the temperature appears distinctly 
when the animals are kept under artificial conditions in cold or 
warm water. 

"In water at 3° C. a dose of 5 centigrams caused only hesi- 
tation in movement and increased motor reflexes at the end of 
six to twenty-four hours. The same result is produced sooner in 
water at 8° C. ; at 32° or 36° tetanic convulsions with death re- 



THEORIES OF ETIOLOGY 79 

suited from even small doses ; and also from the blood of animals 
poisoned by pellagrosein, those injected remained stiff in water 
at 3° and could not leap; at 32° to 36° they were very lively at 
first, but soon became somnolent, though they did not die and 
did not show any tetanic condition ; they succumbed, on the con- 
trary, very quickly with tetanic symptoms, when placed in water 
at 38° to 42° C. 

" For animals kept in lukewarm water the minimum lethal 
dose was 1 centigram per 14 grams of animal weight. The maxi- 
mum dose without death was 50 centigrams per 12 grams of 
animal weight. 

" In general, chickens showed a diminished sensibility to the 
effects of the substances. 

" In the case of a pigeon, death occurred after a dose of 4 
grams per kilogram, with clonic convulsions, preceded by narcosis, 
somnolence, and diminution of temperature. The blood of this 
pigeon, still warm, injected into a frog, produced tetanic symp- 
toms. In the case of hawks, death occurred after a dose of 2 grains 
per kilogram, with diminution of weight, narcosis, and tonic-like 
convulsions. 

" In the case of rats doses of 12 grams per kilogram given in- 
ternally was without results ; on the other hand, the same dose 
administered subcutaneously produced torpor, anorexia, and paraly- 
sis of the hind legs with unilateral contractions ; they fell on the 
right side and when they tried to move they rolled or sometimes 
walked backwards. Later complete paralysis and notable diminu- 
tion of temperature. Convulsions appeared in only two rats after 
the absorption of 2.8 grams per kilogram of the poison. In three 
others with somewhat larger doses, death occurred at the end of 
one to thirteen hours. 

" The autopsy showed hyperemia of the spinal cord, pia mater, 
liver, and kidneys, once also of the lungs ; in one case softening 
of the cord was found. In the case of three out of six of these 
animals, tetanic convulsions appeared, preceded or followed by 
paralysis. Heat seemed to favor narcotics, as cold did tetanic 
phenomena. 



80 A TREATISE ON PELLAGRA 

" An experiment made upon one adult cat only with a sub- 
cutaneous dose of 1.4 grams per kilogram of the most active 
preparation caused death in ten hours. Soon after the injection 
immobility set in with refusal of food and rigidity of the hind 
legs. It was only at the end of three hours that there appeared 
tremor, then tetanic convulsions, hyperesthesia, increase of tem- 
perature (2°) and, two hours later, coma. At the autopsy — 
hyperemia of the brain, spinal cord, liver, and kidneys. 

" In cases of dogs the results were also convincing. With doses 
of 2 grams per kilogram repeated vomiting occurred after a half 
hour to two hours, also contraction of the hind legs, dilated but 
mobile pupils, increase of sensibility and of motor reflexes — two 
hours later general tetanic convulsions, acceleration of the pulse 
and respiration and lowering of temperature. After each attack 
of tetanic convulsions the dog loses his equilibrium, crouches on 
the hind quarters, and presses his head and paws against the 
ground. Experiments with other dogs gave similar results. 

" At the autopsy there was found hyperemia of the meninges, 
optic thalamus, and of the gray matter of the spinal cord ; in 
one case softening of the lumbar cord ; twice ecchymoses of the 
lungs and congestion of the liver; once only hyperemia of the 
entire brain. 

" It is necessary to distinguish three different preparations 
made from the oleo-resin of spoilt corn : that of July and August 
which is very bitter, muddy, chocolate colored, with a strong smell, 
obtained from the corn carried to the state of putrid fermentation ; 
the oil of September, less colored, less bitter, and having a normal 
odor, is extracted from corn less spoilt; finally, the oil extracted 
from yellow bread, which is solid at 19° C, and the oil extracted 
from the embryos of the grain. 

" It was found that in more than a hundred cases in experi- 
ments made during the summer with the active preparations, 
tetanic convulsions appeared at the end of four to ten hours in 
50 per cent of them. The dose of the preparation was .75 gram 
up to 1 gram with animals which weighed between 18 and 35 
grams. To tetanic convulsions succeeded paralysis of the hind 



THEORIES OF ETIOLOGY 81 

legs in 5 per cent, narcosis in 10 per cent; in 30 per cent tetanic 
convulsions did not occur, but difficulty in leaping and exaggera- 
tion of the reflexes of the hind legs at first and later of the fore 
legs occurred. In 20 per cent only narcosis occurred without 
spasmodic symptoms, but death always followed, 

" The same preparation, in dose of 1 gram for 23 grams of 
weight, injected into frogs kept in a room at 8° C. in December, 
produced only mild and retarded symptoms. Tetanic phenomena 
showed themselves at the end of eighteen hours, and at the end 
of thirty hours death occurred. Other experiments in cold or 
warm water demonstrated that the symptoms of poisoning were 
much mitigated by cold. 

" If, before the injection, the heart were laid bare, there was 
found, as in the use of the alcoholic extract, that at the end of 
a half hour a retardation of the pulse occurred most marked on 
the appearance of tetanic phenomena. 

'' The same tetanic phenomena appeared after injection was 
made in a rat whose brain had been removed; partial section of 
the cord prevented spasmodic phenomena on the corresponding 
side. The members remaining in nervous connection with the 
rest of the body, but not with the circulation, exhibited constantly 
tetanic symptoms. 

" The urine and blood of animals having had injections of the 
alcoholic extract as well as the oil, produced tetanic phenomena in 
frogs, though the animals themselves remained free from toxic 
symptoms. 

" The experiments on chickens are important because of their 
duration. In one chicken with a subcutaneous injection of the 
oil there were no motor symptoms ; but it was droopy all day 
and had diarrhea. A cock behaved in the same manner. When 
given by mouth, this substance had a less marked effect; how- 
ever, it arrested increase in weight in young fowls. In one un- 
treated chicken the weight increased 200 grams from the 20th of 
November to the 2nd of December, but under treatment with the 
oil from the 3rd to the 16th of December the increase of weight 
was only 100 grams. Finally, after five months of interrupted 



82 A TREATISE ON PELLAGRA 

administration of the oil, there appeared choreiform movements 
of the head, previously observed in the experiments with Dupre. 
In the case of one chicken choreiform movements of the head 
appeared at the end of ten days ; with repeated doses the motor 
derangement became general — it walked backwards, raised the 
feet slowly and in an exaggerated manner, and had a tendency 
to walk very near the wall. Then eczema of the comb appeared 
with diarrhea, increase of temperature after the injection, defer- 
vescence in the intervals; the chicken died with typhoid and 
paralytic phenomena. At the autopsy were found intestinal 
hemorrhages similar to those seen in septic poisoning. 

tk With four rats one dose of 5 grams brought about subnormal 
temperature with paresis, contractures, and once death following 
paralysis of the hind legs. A cat, after a dose of 4.9 grams per 
kilogram, had photophobia and refused food. With larger doses 
(6 grams) loss of appetite, paresis, decided photophobia and death 
at the end of two days, with loss of 40 per cent in weight. 

"In the case of a bitch, after an injection of 20 grams, tonic 
convulsions of the legs and paresis occurred in two hours. Three 
hours afterwards there remained only a decided reflex excitability, 
mydriasis, agitation, refusal of food, and staggering gait. The 
next day there remained only difficulty in leaping and walking, 
with rigidity of the fore legs. In another dog, after an injection 
of '30 grams, torpor, rigidity of the hind legs, and slight desire 
for food. In general, the oil produced the same symptoms as the 
alcoholic extract, although less in degree. 

" The oil of moulded bread produced the same symptoms as 
the maximum grade of oil of corn prepared in August. In a 
single experiment it was more active." 

The oil made from the embryos of spoilt maize caused symp- 
toms similar to those produced by oil made from the entire grain, 
but the effect was not so marked. 

The effect of the aqueous extract was similar to that of the 
alcoholic extract, but not so decided. 

The alkaloid was removed by Erba from the oil. When injected 



THEORIES OF ETIOLOGY 83 

into frogs it produced tetanic convulsions. Lombroso claimed 
that the residue after the extraction of the alkaloid still produced 
tetanic symptoms in the frog and inferred from this that there 
was more of a poisonous nature in spoilt corn than this strychnine- 
like product. 

Pellizzi 1 studied sound corn meal and found that an article 
counted of this type often contained more micro-organisms than 
another appearing much less sound. He thought that to insure 
a safe food it would be necessary to dry the grain in an oven 
at 70° C. He concluded that the important organisms of spoilt 
corn resemble the putrefactive type, because symptoms said to be 
analogous to pellagra were produced in dogs by such cultures. 
He thought also that the results could be attributed exclusively to 
putrid substances and not to a specific poison of spoilt maize. 
The pellagrous manifestations produced in dogs by the intravenous 
administration of 10 grams per kilogram of body weight of an 
aqueous extract of polenta which was contaminated with certain 
micro-organisms were pareses, gastro-intestinal disorders, and 
psychic confusion. 

Marie concluded his discussion with these significant utterances : 

" The facts recognized by statistics and by clinical observation are 
not always easy to reconcile. The statistics show that only in 
the case of 25 per cent of pellagrins can it be affirmed with 
certainty that they were nourished with food consisting principally 
of corn very badly spoilt. On the other hand, clinical observations 
demonstrate that it is not rare to see cases of severe pellagra 
in persons well nourished and in good circumstances, of whom it 
can be said that they do not habitually eat spoilt corn. Finally, 
there are recrudescences of pellagra with grave symptoms when 
the convalescents return to nourishment with corn, even when the 
corn consumed answers to the most severe hygienic demands. 
" These experiments prove the existence of micro-organisms 

1 Pellizzi, G. P., " SulP etiologia della pellagra in rapporto alle sostanze 
tossiche prodotte dei microorganismi del maiz guasto." Ann. di freniat, Turin, 
1893-94, IV. 



84 A TREATISE ON PELLAGRA 

either in a developed form or in the form of spores in the grain 
and meal of corn which have the very best appearances and are 
habitually used for human food. It can then be supposed that 
the elements necessary to the production of the pellagrous symp- 
toms;, once having entered into the circulation, are there decom- 
posed under the action of ferments found in the organism, and 
undergo, after absorption, toxic transformations. It cannot be 
determined, according to Pellizzi, what is the nature in a given 
medium of the products of the bacteria found on corn. Do they 
constitute a chemical poison in the strict sense of the word ; or, as 
is more probable, do they belong to the amorphous chemical fer- 
ments, which can be produced at a determined phase of their 
development? For many similar ferments complex actions have 
been found; Pellizzi found them in his extracts of corn. It is 
reasonable that the harmful effect does not come from a pure 
culture of one organism, but from a mixed culture of several 
varieties. It is a question, certainly, of a combined and probably 
mutual action, not yet denned. If a toxic substance could be 
directly drawn from edible corn without mixture with putrid 
substances in the strict sense of the word — then the features of 
pellagrous poisoning can represent a poly-toxic state. Finally, it 
is necessary to take into consideration the most complex and 
various facts and to give to spoilt corn a very wide definition. 
Almost all corn, with few exceptions, can thus be considered 
spoilt corn to some degree. Corn, absolutely sterilized, if one 
could have it, would certainly be harmless, and, of course, the 
meal also. But if it is difficult to have corn entirely dry, it is 
certainly impossible to keep it in this state, for as soon as the 
places in which it is stored reach a certain degree of humidity, 
the most diverse micro-organisms find favorable conditions for 
their development. 

" In concluding his experimental work Lombroso states that 
' with, such evidence as has been submitted it does not seem 
longer possible that the specific cause of pellagra can be doubted, 
and it is certain that the etiology of other maladies can present 
documents neither more numerous nor more convineinoy ' 



THEORIES OF ETIOLOGY 85 

Probably no work on the subject of maize as an etiological 
factor in the production of pellagra has yet been done of so 
great importance as that of Tizzoni who claimed to have isolated 
from the blood, cerebro-spinal fluid, feces, and organs at autopsy 
of pellagrins, a specific micro-organism, called by him the strepto- 
bacillus of pellagra. The same organism was also found in certain 
samples of spoilt maize. This investigation extending over a 
period of ten years was of the most exhaustive character and 
bade fair at first to settle the mooted point, but it has not been 
received with much enthusiasm and there are serious objections 
made to it. It has been my privilege to verify the greater por- 
tion of Professor Tizzoni's claims in my own laboratory in Ivforth 
Carolina. At the outset it should be said that this organism is 
not the bacterium maidis or potato bacillus, as some American 
students have seen fit to designate it. The organism was first 
isolated from the blood of patients with the acute or typhoid type 
of the disease. In 1907 it was shown that the disease could be 
experimentally produced in guinea pigs, provided maize was 
added to the diet; when the maize was omitted the disease could 
not be produced. The following hypotheses were advanced by 
Tizzoni : 

(1) The germ is the same in both the acute and chronic types 
of pellagra. 

(2) In the acute type the germ is found in the blood where 
it reproduces itself. 

(3) In the chronic type of the disease it is limited to the 
digestive tract, 

(4) The toxins produced in the digestive tract are modified 
perhaps by the blood serum or white blood corpuscles before reach- 
ing the nervous system. 

(5) Maize is either a suitable culture medium or acts as 
a means of transmission of the germ. The germ is propagated 
by fertilizing the maize crop with the dejecta of pellagrinous 
animals. This germ is more active when the grain is not properly 
matured. 

This work was based on the acute type of the disease; on 



86 A TREATISE ON PELLAGRA 

the chronic not enough has been done to draw any reliable con- 
clusions. The author drew an analogy between acute and chronic 
pellagra and acute and chronic tuberculosis. Acute tuberculosis, 
he said, was the final stage of the chronic. This conclusion has 
been proven incorrect in the southern states where the acute form 
of pellagra has been primary in many accurately reported cases. 
This was the experience of Searcy in Alabama and was my own 
experience in North Carolina. Such a condition as this acute 
primary pellagra seen by us in this country is unknown in 
Europe where the very word bears the impression of a chronic 
disease. We must take exception also to the explanation that 
the grain became contaminated by the organism in question 
through the fertilization of the maize with animal excreta. This 
can be readily disproven by the fact that maize in the United 
States is not so fertilized except in very isolated instances. 

Tizzoni's organism was obtained from the blood of animals 
which had been inoculated with the blood of patients suffering 
with acute pellagra. This organism can be cultivated indefinitely 
on defibrinated rabbit's blood by renewing the culture every thirty 
or forty days. When it is so cultivated the form is very char- 
acteristic. Chains are found to predominate. Great variations in 
size and morphology are noted. The organism is quite small 
and at first sight appears as a streptococcus, but is really a 
bacillus, though a very short one; hence the name given by 
Tizzoni — the strepto-bacillus of pellagra. When transplanted 
from the rabbit's blood serum to agar-agar or beef broth the 
chains are found to be made up of larger elements. Often there 
is an occurrence in pairs and an appearance of a lanceolate bacillus 
similar to the pneumococcus of Frankel. At first considerable 
difficulty is found in growing the organism, but it soon becomes 
accustomed to saphrophytic life and grows readily on agar-agar 
while at first it would only grow on non-coagulated albumens. 

The most important characteristic of this organism was that 
it was able to resist unusually high temperatures. A culture in 
agar-agar twenty-four hours old was obtained from a blood serum 
culture. Half of it was kept as a control and the other half 



THEORIES OF ETIOLOGY 87 

was divided and exposed for one hour to 60, 70, 80, and 90° C. 
respectively. The tubes exposed to 60° and 70° grew as well as 
the control. The 80° tube grew slowly, while the one exposed 
to 90° remained sterile. Such a resistance to heat in an organism 
not bearing spores is unique, though something of the same nature 
is said to be possessed by the bacterium maidis. It was noted 
that this culture, which had been exposed to 90° C. for one hour 
and which would not grow, when injected into a guinea pig would 
produce death, not by a toxemia but by the growth of the living 
organism. In such cases the organism which has been exposed 
to this high degree of heat may be further propagated by passing 
through the guinea pig, and this is a valuable way of securing 
a pure culture. Suspected material is heated to 90° C. for 
one hour and a portion of the heated material is injected into 
the guinea pig and the pure culture of the strepto-bacillus of 
pellagra is recovered from the blood. It is readily appreciated 
that such an organism could easily retain its life in many in- 
stances in polenta. This dish of the Italian peasantry is often 
very imperfectly cooked and it has been shown that corn meal 
has a property of " balling," that is, of forming masses when 
mixed with water. Wheat flour does not have this property, 
but at once when brought in contact with the water forms a 
homogeneous suspension. It was thought that these polenta balls 
could easily harbor in the center this organism which had not 
been exposed to as much as 90° of heat. In one isolated instance 
death occurred by the injection of a culture which had been ex- 
posed to 100° for one hour. 

It was shown that in the experimentation with this organism 
given by the mouth, which is assumed to be the manner in which 
the infection occurs, the disease could not be produced unless 
the animal was fed maize at the same time. One group of animals 
was fed the organism without corn food and remained healthy; 
a second group was fed the same corn without the organism and 
remained healthy; a third group was fed the organism with corn 
food and all died with symptoms supposed to be those of pellagra. 
It was evident from this that the corn was essential either by 



88 A TREATISE ON PELLAGRA 

making a predisposition or by furnishing a suitable nutritive 
medium. It was then tried to see if animals fattened on maize 
which was later withheld from the diet and then these same 
animals inoculated with the streptococcus could be infected. 
Such animals were infected and died in from sixty-six to seventy- 
two days. The conclusion from this result was that corn pre- 
disposed to the disease. 

The rabbit was found to be immune to subcutaneous injections 
and showed only a slight reaction to the gastric method of in- 
fection. A slight diarrhea was the only result. 

An effort was made to test the property of vaccination with 
this strepto-bacillus. Robust guinea pigs were subcutaneously 
inoculated with twenty-four-hour-old agar-agar cultures subjected 
to 90° C. for one hour. The dose was gradually increased and 
the intervals varied from five to ten days. The animals were fed 
ordinary food and the weights increased. But none of these 
animals were able to resist gastric infection, all of them dying. 
This experiment at least showed that a tolerance was acquired 
by beginning with small doses. It was seen that animals which 
had been vaccinated did not survive mouth infection as well 
as those not so treated ; the former died in a shorter time than 
the latter. This was supposed to be due to anaphylaxis. 

The feces in chronic pellagra was found to contain the organism 
and it was possible to reproduce the disease in guinea pigs by the 
inoculation of fecal matter which had been exposed to 80° C„ 
for one hour. In the chronic form the organism was not re- 
covered from the blood as in the acute. It was seen that all 
diarrhea in pellagra was not specific, but that pellagrins were 
very susceptible to diarrhea on the slightest provocation, such as 
a change in food. 

Spoilt -corn was found at times to contain the same strepto- 
bacillus and its virulence was greatly enhanced by passing it 
through the guinea pig as above mentioned. All the tests made 
with the organism obtained from the grain showed that it was 
the same as that isolated from the blood in the acute type of the 
disease. Tizzoni found the organism in nine samples of what 



THEORIES OF ETIOLOGY 89 

he considered bad maize, but in nine samples of sound maize it 
could not be found at all. An organism was found in good corn, 
but it was proven not to be the strepto-bacillus by the fact that 
it did not resist a temperature of 80° C. for one hour. Should it 
be proven that this is the specific cause of pellagra, it would be a 
simple matter to test all corn by this heat isolation process. A 
portion of the suspected corn by this method is placed in a 
tube of bouillon and placed in the incubator at 37° C. for twenty- 
four hours or longer. This gives sufficient time for the develop- 
ment of a sufficient number of organisms. The culture is then 
subjected to a temperature of 80° C. for one hour and later 
a culture made from this heated culture will demonstrate the 
presence of the strepto-bacillus. To be more accurate it is well 
to subject the corn culture, after allowing a growth to occur, 
to a temperature of 90° C. for one hour and then, taking a 
portion of this heated culture and passing it through a guinea pig, 
to await the development of the symptoms supposed to be 
pellagrous. 

It has never been proven whether or not this organism of 
Tizzoni can be found on other grains, as wheat, barley, or rye. 
It also remains to be proven if there is any other way of infection 
besides the mouth. 

Tizzoni showed that in animals which he had infected with 
his organism he could effect a cure by the injection of the 
blood serum of healed pellagrins. A group of control animals 
not so treated invariably died, while all of the treated animals 
recovered. 

The conclusions of Tizzoni were as follows : 

(1) The same organism isolated from acute pellagra can be 
isolated from the blood of chronic pellagrins as well as from the 
feces. It was also found occasionally in bad maize. 

(2) The organism was a non-spore bearer and resisted a tem- 
perature of 80° and even 90° for one hour. 

(3) Cultures from different sources have different character- 
istics but can be readily distinguished. 

(4) Morphological and bacteriological characteristics demon- 



90 A TREATISE ON PELLAGRA 

strated in bouillon and agar-agar cultures differ according to 
virulence and degree of attenuation. . 

(5) The organism introduced into the stomach is pathogenic, 
provided corn is fed at the same time. 

(6) The disease experimentally produced in the guinea pig 
was similar to that occurring in man. This was especially seen 
in the tardiness of the infection, the symptoms, and the organic 
lesions. The point of election of the organism in the guinea pig 
was the intestine. The intestinal changes were of a destructive, 
hemorrhagic character, accompanied by a general intoxication, 
whose effect was chiefly on the nervous system, the blood vessels, 
the red blood corpuscles, and secondarily on the liver and kidney. 

Tizzoni's work was the most important ever done on the specific 
cause of pellagra linked with the deterioration of maize. It did 
not produce so much of a sensation as did the work *of Lombroso, 
but his results were much more convincing. The reaction pro- 
duced by the action of the blood serum of healed pellagrins on 
guinea pigs experimentally inoculated was, at least, very sug- 
gestive. But the whole question depends on the identity of the 
condition produced by the action of the strepto-bacillus. It seems 
more reasonable to suppose that the symptoms produced by this 
organism were more nearly pellagra than the symptoms produced 
by Lombroso. It becomes necessary to again consider the question, 
Can pellagra be produced in the lower animals ? The most im- 
portant work on this subject was done by Lavinder and Anderson 
in the laboratory of the L T nited States Public Health and Marine 
Hospital Service. Their work was done on the rhesus monkey, 
using material from acute cases of pellagra. In all but one case 
of a number of experiments the results were negative. In this 
one case the results were not positive enough to justify any valu- 
able conclusions ; it was merely suggestive. 

Being deeply impressed with the work of Tizzoni, I spent two 
years experimenting with the same organism. Through the 
courtesy of Professor Tizzoni I was able to secure a couple of 
preparations of his organism. It was not difficult to isolate the 
same organism here, both from the acute cases and from the 



THEORIES OF ETIOLOGY 91 

maize. After a careful study the only conclusion that seems 
justifiable is that the disease produced by the strepto-bacillus of 
pellagra (Tizzoni) was not pellagra. It was my experience in 
a large number of acute cases that the cultures remained sterile 
when clinically there was every reason to expect a growth and 
the reverse was occasionally the case. The finding of the organism 
was so uncertain that another source of its occurrence was sought. 
It seemed reasonable at one time to suspect that this organism 
was merely a skin contamination. The results in my laboratory 
were not sufficiently conclusive to be of any value and the work 
was abandoned, though I have seen falling of hair and emaciation 
in a guinea pig, and death, and the autopsy finding of a perforated 
bowel. All of the postulates of Koch were satisfied, but even the 
most important link in the chain was lacking — the establishment 
of the identity of this condition with pellagra in man. 

Babes and Manicatide, Antonini, and Mariani, from experi- 
ments performed by them respectively, concluded that there ex- 
isted in the blood of cured pellagrins a specific antitoxin against 
the poison of spoilt maize. 

The toxico-infective theory was that there was formed in the 
body from spoilt corn certain toxic substances or endogenous 
toxins and that the disease was a sort of auto-intoxication or 
possibly an intestinal mycosis. ISTeusser thought that there was 
formed in corn a " receptive mother substance," x due to the 
bacterium maidis which underwent in the intestinal tract a 
change and became toxic. De Giaxa 2 and Di Donna thought 
that the common colon bacillus became greatly modified by 
its contact with maize. It then became responsible for the 
disease. 

In 1902 Ceni attributed the cause of pellagra to the asper- 
gillus fumigatus and the aspergillus flavescens and developed a 
theory that an attack of pellagra at one season was due to a par- 

1 Neusser, E., " Untersuchungen iiber die Pellagra," Wien. Med. W\ochr., 
1887. Also, Neusser, E., " Die Pellagra in Oesterreich und Rumaenia." This 
report was also read before the K. K. Arztliehe Gesellschaft in Vienna, Jan., 
1887. 

2 De Giaxa, "Pellagra," Manuale d'igiene pubblica, 1890-1892, 



92 A TREATISE ON PELLAGRA 

ticular fungus, while an attack at another season was due to the 
other. lie found the aspergillary infection usually in the lungs, 
pleura, pia mater, pericardium, and mesenteric glands. The 
aspergillus fumigatus was the more pathologic and had its period 
of activity in the spring, while the aspergillus flavescens displayed 
its activity in the fall. He thought that maize was not an essen- 
tial but that the moulds in question found it a much more suitable 
culture medium than any other grain, and when the growths 
occurred on maize their toxicity was increased. 

Another notable contribution to the study of the etiology of 
pellagra was made by Neusser of Vienna, who was delegated by 
the Austrian government to report on pellagra in that empire and 
in Roumania. He began this report by the statement that maize 
was the cause of pellagra because the disease did not appear in 
any section until after the introduction of the American cereal. 
Some of his observations would tend to strengthen the claim 
of Sambon, which will later be referred to at length. Xeusser 
did not believe in the theory of the insufficiency of maize be- 
cause he failed to find pellagra in many countries where the people 
were very poor and the food was exclusively of maize, rice, or 
potatoes. The scourge was generally disseminated all over Rou- 
mania among well-nourished people who ate besides corn, meat, 
vegetables, and dairy products. In this his observations are in 
accord with our observations in Xorth Carolina, as stated on a 
previous page. Xeusser said that corn did not contain the pella- 
grinous substance or poison, but the mother substance (substantia 
mater), which in a normal condition of the digestive apparatus 
is digested or eliminated without any damage to the organism, 
but if the digestion is disturbed and the digestive secretions altered, 
there results abnormal fermentation processes, and then in such a 
medium this mother substance becomes a veritable poison. In 
this manner he explained the fact of the immunity of almost all 
domesticated animals to the supposed poison of maize ; the com- 
parative tolerance of children for the same poison; the fact that 
pellagra appears in so many different periods of life ; and the 
fact that some tolerate bad polenta for a long life and finally in 



THEORIES OF ETIOLOGY 93 

old age succumb ; and finally in some families with numbers of 
members oftentimes only one will be affected. lie claimed that 
all of these facts argued against a pure toxic or intoxication 
theory. He came then to the conclusion that the disease was 
the product of two factors. One was to be found in the deteriora- 
tion products of the corn and the other in the condition of the 
organism, hence he regarded pellagra as an auto-intoxication. The 
deleterious substance contained in the maize was regarded as a 
glucoside substance, which became active only in an abnormal 
state of the digestive tract. Alcohol was thought to play an im- 
portant part by producing a gastroenteric catarrh and by a 
depressing effect on the organism. But the effect of alcohol 
generally was not considered ; it was thought that the trouble 
lay in alcohol made of maize which had become deteriorated. 
All alcohol in Roumania is made from maize, according to 
iveusser. In his chemical studv he found in damaged corn a 
substance which had the characteristics of an aldehyde and which 
he thought arose from the decomposition of more complicated sub- 
stances as resins and giucosides. He also thought that it was 
possible for other cereals to contain pellagrous material. He con- 
cluded his report with the statement that the toxic principle owes 
its origin to substances which in themselves are not poisonous 
and which are probably developed through the action of the bac- 
terium maidis. As a prophylactic recommendation to the Austrian 
government he offered the following: 

(1) To cultivate only that variety of corn which matures 
quickly and thoroughly. 

(2) To adopt, as Italy had already done, the drying apparatus 
for corn intended for food in order to prevent the development of 
the bacterium maidis. 

(3) To establish according to the Mexican system stores for 
the preservation of maize which shall be under control of the 
government. 

(4) To encourage the cultivation of other grains and also 
vegetable food. 

(5) To improve the purity of portable waters. 



94 A TREATISE ON PELLAGRA 

(6) To establish colonies for the employment of pellagrins with 
suitable pursuits. 

(7) To improve the sanitary conditions in that region between 
the sea and the Italian frontier. 

In 1890 there appeared the report of Gaetano Strombio, Jr., 1 on 
the sanitary aspects of the pellagra problem in Italy. It is a 
report of great exhaustiveness, going into the laws and provisions 
for the proper care of maize. 

Raubitschek 2 applied the biologic, serologic, and anaphylactic 
deviation of the complement as well as other means to test the 
basis of the various theories of the etiology of pellagra. He de- 
cided that none of the theories were reasonable. He tried to 
show that pellagra and beri-beri were the result of the action 
of some toxin in maize and rice which must be sensitized by the 
chemical rays of the sunlight before any toxic action can be 
displayed. He found that animals fed corn and rice did not 
develop symptoms until exposed to the sunlight, when there soon 
appeared emaciation and paralytic symptoms which resulted in 
death after a period ranging from eight to twenty-one days. Ani- 
mals removed from the sunlight early in the disease process 
promptly recovered, even though the diet remained unchanged. 
He concluded that pellagra was an alimentary poison, which re- 
quired the addition of sunlight before it became active. Some 
of these experiments were performed with buckwheat. Animals 
so fed and kept in the dark developed no symptoms, but when 
exposed to sunlight the hair fell out and emaciation and paralysis 
resulted. This condition, which is known as fagopyrism, is 
strikingly similar to pellagra, especially in regard to the seasonal 
variations and the occurrence of the skin disturbances on the parts 
exposed to sunlight. He thought that the pellagra toxin developed 
in those parts of the skin exposed to sunlight " from the action 
of the chemical rays on the lipoid, alcoholic-soluble element in 



1 Strombio, Gaetano, Jr., " La Pellagra I Pellagrologi e le Amministrazioni 
Pubbliche. Saggi di Storia e di Critica Sanitaria." Milano, 1890. 

2 Raubitschek, Editorial in Jour. Am. Med. Assoc, LV, and quoted by Lavin- 
der and Babcock in the translation of " La Pellagra," by A. Marie. 



THEORIES OF ETIOLOGY 95 

corn." There is still a large field for research in order to deter- 
mine the toxicity of corn, and until more work of this nature 
is done there must remain a doubt in the minds of many re- 
garding the nature of the poison which produces the various 
symptoms recorded in the lower animals. At this time it cannot 
be said that pellagra has ever been produced experimentally. 

Black and Alsberg 1 state that the tests for the acidity of corn 
are very important and in a measure, at least, determine the 
noxiousness of the grain. It may be that this acidity about which 
they speak below may account for the symptoms produced in the 
lower animals without necessarily being connected with pellagra. 
They say: 

" Much stress is laid in Italy upon the determination of toxicity. 
Schindler does not even mention it. It is performed as follows: 
A weighed quantity of meal is extracted at about body temperature 
with 90 per cent alcohol for twenty-four hours. It is then filtered 
and the alcoholic filtrate evaporated until the alcohol is removed. 
The residue is taken up in water at a temperature of 40° C, 
made up with warm water to a definite volume so that 0.5 c.c. 
corresponds to about 0.5 grams of the meal, and an amount 
equivalent to 0.5 grams of meal injected subcutaneously into a 
mouse. Large quantities of liquid are often injected, but this 
seems open to objection in so small an animal. The mouse is 
chosen because it is supposed to be the most sensitive to the poison. 
The symptoms are described as consisting of clonic spasms and 
localized contractures of the muscles, embarrassed respiration, 
gradual paralysis, collapse, and death. Sometimes opisthotonus 
ensues. On autopsy little is said to be noticeable except in- 
flammation at the site of injection and hyperemia of the 
cord. 

" A sample of corn which was toxic when injected in the 
dosage given above was never encountered in the present investi- 

1 " The Deterioration of Maize with Incidental Reference to Pellagra," by 
O. F. Black and C. L. Alsberg. U. S. Department of Agriculture, Bureau of 
Plant Industry. Bulletin No. 199. 



96 A TREATISE ON PELLAGRA 

gation. However, the procedure was varied from that of the 
Italians because of the following considerations: The extracts 
may be very acid. It is well known that herbivorous animals are 
very sensitive to acids which they are incapable of destroying in 
their metabolism. The symptoms of such an acid intoxication 
(acidosis) are, however, different from those described above. 
The behavior of mice toward acid intoxication is not known so 
far as a hasty search of the literature has shown. It is therefore 
conceivable that some of the toxic effects of the injection of corn 
extracts may merely have been acid effects. For these reasons 
the solutions injected were usually neutralized. Perhaps that is 
why toxic effects were not obtained. In this connection if is 
interesting to note that Gosio and Ferrati distinctly state that 
alkali neutralizes the poison, and in another place that culture 
fluid of the Penicillium cultures become less toxic as the culture 
grows older and their acidity diminishes." 

It is very probable that this acid quality of maize has been 
responsible for the pathologic effect produced in the laboratory 
animals after the feeding of corn, as previously described. As 
mentioned in the preceding chapter, the most important work 
yet done was that of Lavinder and Anderson in their study of 
the question of the transmissibility to the lower animals. • The 
animal used by them was the rhesus monkey, but the results did 
not strengthen their belief in this possibility. It is hardly fair 
to accept any of the experimental work done on the lower animals 
because of this defect. Some other means must be found to 
establish the identity of these various conditions with pellagra 
before there can be any value in the conclusions. It does not 
seem to be a difficult matter to find causes for the disease con- 
ditions in the laboratory animals other than the possibility of 
pellagra. There are many forms of grain poisoning besides 
ergotism, and granting for the sake of argument that bad maize 
causes pellagra, it is probable that it also causes other forms 
of poisoning. Thus, it might be worth the time of some investi- 
gator to prove that the causes of death in fowl and cattle as well 



THEORIES OF ETIOLOGY 97 

as laboratory animals can be explained without incriminating 
pellagra. 

The most startling theory of the etiology of pellagra was made 
by Professor Louis W. Sambon of the London School of Tropical 
Medicine before the British Medical Association in 1905 at the 
Leicester meeting. At this time he stated that he believed pellagra 
to be an insect-borne parasitic disease and that the specific parasite 
might be a protozoal organism. In 1910, at a meeting of the 
Pellagra Investigating Committee, he developed this idea by sug- 
gesting that the insect might be a Simulium. This hypothesis 
was founded on topographical and epidemiological facts. In 1900 
and 1903 he visited some of the pellagra-affected districts of 
northern Italy where his first observations were made. This 
work is of so great importance and conforms so closely to the 
actual situation in North Carolina that it will be referred to 
here at great length. Sambon's report 1 brought forth a great 
torrent of objection and even of abuse. In this country many who 
had no right to any opinion denounced it as a hoax, and one ele- 
mentary student of the disease went so far as to diagnose the 
condition of the eminent authority on tropical diseases as hysteria. 
But the earnest endorsement of such a student as Sir Patrick 
Manson more than over-balanced the opinions of these lesser lights. 
~No theory has yet been advanced which so well fits into the real 
facts. In this theory it is at once appreciated that the author- 
of it does not make the disease fit the theory as do the zeists, 
but the theory is the result of the most careful observation made 
in a scientific way and without bias. 

He said in the beginning of his report : " The recent investi- 
gation carried out on behalf of this committee substantiates my 
suggestions, and, in my opinion, demonstrates the reliability of 
topographical and epidemiological data when correctly interpreted. 
In 1903, availing myself of similar data, I was able to infer 
that sleeping sickness is a tsetse-borne disease, and to indicate the 
very species of the carrier — Glossina palpalis — conclusions 

1 Sambon, L. W., " Progress Report on the Investigation of Pellagra." Jour- 
nal of Tropical Medicine and Hygiene, 1910. 



98 



A TREATISE ON PELLAGRA 



which subsequent investigations in Africa have fully established." 
His investigations were made in Italy in the provinces of Milan, 
Bergamo, Brescia, Padua, Rome, and Perugia. 

In this report he took up the various theories and considered 
them in a systemic manner, thus: 

The present theories of the etiology of pellagra now in vogue in 
Italy are as follows: 




Fig. 2. — Peculiar Bodies Found in Nuclear Material from Cerebro-spinal 
Fluid, in Smears from the Sensorio-motor Cortex and from a Blood Clot 
Lying in Contact with and Posterior to the Lower Cervical and Upper 
Dorsal Regions of the Spinal Cord. (Reproduced by courtesy of Professor 
Sambon. London Jour, of Trop. Med. & Hygiene, Dec. 15, 1911.) 

(1) Insufficiency of nutriment, owing to poverty, inappropriate 
food (maize), and lack of wine. 

(2) Toxicity of maize, especially when used exclusively as an 
article of diet. 

(a) Owing to specific toxins normal to this cereal, even when 
of good quality and perfectly sound. 

(5) Owing to toxic substances produced at spring time, dur- 
ing the process of germination. 

(c) Owing to toxic substances resulting from the action of Ba- 
cillus coli on sound maize, within the alimentary canal, after 
ingestion. 



THEORIES OF ETIOLOGY 99 

(d) Owing to toxic substances elaborated during the decom- 
position of maize. 

(I) By the common blue mould, Penicillium glaucum. 

(II) By certain particular strains of P. glaucum. 

(III) By several kinds of fungi and bacteria. 

(3) Parasitism of certain organisms ingested with either sound 
or deteriorated maize. 

(a) Certain fungi: Aspergillus fumigatus and A. flavescens. 

(b) Strepto-bacillus pellagrae, an organism which Professor 
Tizzoni claims to have isolated from the blood, cerebro-spinal fluid, 
tissues, and feces of pellagrins, as well as from damaged maize. 

(4) Parasitism of a nematode worm, belonging to the family 
Filariidae, which Professor Alessandrini claims to have found 
in the skin of pellagrins and in the drinking water of affected 
districts. 

All but this last mentioned are different phases only of the 
maize theory. 

Sambon says the relationship of cause and effect between maize 
and pellagra is based on the following assumptions : 

(1) The disease appeared for the first time in Europe soon 
after the introduction of maize from America. 

(2) It followed everywhere the extension of maize cultiva- 
tion, and increased pari passu with the more general adoption 
of the new cereal as an article of food. 

(3i) It occurred only in places in which maize is either grown 
or imported, and exclusively in people who use it as an article 
of food. 

It is stated that the maize theory is supported by the belief 
that the disease has been diminished by the adoption of preventive 
measures. These measures are : 

(1) The inspection of maize, and seizure of all unsound grain 
and its products. 

(2) The exchange of deteriorated maize for good maize. 

(3) The providing of drying apparatus for damp maize. 

(4) The providing of suitable bakehouses in rural districts 
for the proper baking of maize bread. 



100 A TREATISE ON PELLAGRA 

(5) The abolition of late varieties of maize which do not ripen 
properly. 

(6) The compulsory notification of all cases of pellagra. 

(7) The obligation, in all affected districts, upon the municipal 
authorities to supply free meals to all their pellagrins twice every 
year for periods of not less than forty days. 

(8) The institution of special retreats, " pellagrosari," for the 
housing, feeding, and treatment of the more advanced cases. 

(9) The dispensation of free salt to all pellagrins and their 
families. 

The following facts were thought by Sambon to argue against 
the maize theory : 

(1) There is no foundation whatever for the belief that pellagra 
broke out in Europe soon after the introduction of maize from 
America. 

(2) The topographical distribution of pellagra does not coin- 
cide either with the distribution of the maize cultivation or with 
that of maize consumption. 

(3) The disease occurs frequently in persons who have seldom 
or never partaken of maize as an article of food. 

(4) All preventive measures based on the maize theory have 
failed. 

(5) The characteristic skin eruption and other symptoms of 
the disease may recur each spring for several successive years in 
patients who are far removed from the endemic districts and who 
abstain from maize. 

Sambon thought that maize was introduced into Europe from 
South America by the Spaniards soon after the discovery of 
America. The proofs that this grain was introduced from Asia 
at a much earlier date are not considered sufficient to establish 
the claim. He further mentioned that he found the names 
" melega," " melica," and " formentone " used to designate maize 
as early as the middle of the sixteenth century. Savonarola in 
1554 stated that bread made of " melega " was less nourishing 
than any other kind and very indigestible. There were many 
other references to writings of the sixteenth century which proved 



THEORIES OF ETIOLOGY 



101 



that maize was an article of food at that time, though it had 
not come into such general use as it did later. It was used by 
the peasantry chiefly in times of scarcity and found its use chiefly 
as a food for fowls and other animals. 




Fig. 3. — Professor L. W. Sambon Holding a Three-tear-old Pellagrin. 



It must be admitted then that if Casal's work indicated the 
appearance of a new disease in Europe it did not accompany the 
introduction of maize into the same territory, for we have seen 
that this grain was used as a food for a century and a half and 
in some instances two centuries before the date of the earliest 
record of pellagra. There is no way in which these two events 
can be connected, for any one who has read Casal's work will be 



102 A TREATISE ON PELLAGRA 

at once impressed with the important fact that in 1 7 ; J 5 he had 
been observing the disease for many years and he never claimed 
priority in recognition or in the naming of the scourge. One 
would infer that in his time there was as much disagreement 
regarding the nature of the disea.se as there is to-day. .Maize has 
been used in the United States as far back as our records go, and 
in Pern there are many evidences thai ii was an article of food 
many centuries ago, but with as much certainty we can say that 
pellagra has existed in this country only for a comparatively short 
period, even if we accept many unproved statements of its earlier 
appearance which are nol recorded in the literature. As stated 
in the preceding chapter, the old writer- on natural history of 
this country did not mention pellagra or anything akin to it, 
though the same writers did accurately describe uncinariasis. 

He then shows many evidence- of the fact that pellagra does 
not confine its activities to those who have eaten maize. The 
disease is shown to occur in countries where it is neither grown 
nor eaten. Such instances were found in his experience in Spain 
and France and in my own experience in this country. At a 
meeting of the Catalonian Academy of Medicine, Casana stated 
that the sad boast of the greater prevalence of pellagra belonged 
to those provinces in which the use and cultivation of maize were 
unknown. We read further in this exhaustive report many in- 
stances, even in Italy, of the fallacy of the maize theory. It would 
seem that one authentic case in which it could be shown con- 
clusively that maize was never eaten would be enough to bring 
about a renunciation of the theory, but such has not been the 
ease. I have selected only a few examples from Samhon's long- 
list to add to my own previously mentioned cases. Doctor Conti, 
chief medical officer of the Province of Ravenna, said that pellagra 
was not confined to the small mountainous region where maize 
is eaten, but also in the district of Lugo where it is not eaten. 
In 1903, Garbini described five typical cases of pellagra under 
the name pseudo-pellagra because the patients were lunatics who 
had never eaten maize. This is a very significant utterance and 
deserves a careful consideration in this connection. He said : 



THEORIES OF ETIOLOGY 103 

" Although all the symptoms indicate pellagra, in view of our 
present knowledge concerning its etiological factors we cannot 
consider our patients to be pellagrins. The entire absence of the 
etiological element of pellagra, as also the fact that they are not 
the progeny of pellagrins, dissuade us from forming such a diag- 
nosis and confirms us in the belief that the dread disease does 
not occur in Sicily. It is a well-known fact that in this island 
maize is neither grown nor imported from abroad for local con- 
sumption, since it is neither eaten in the form of polenta nor in 
that of bread. Only very exceptionally it is eaten grilled on a 
charcoal fire. The Sicilians, says Tonini, may be extremely poor, 
indeed, they may live solely on the parings of prickly pears, but 
they will never eat maize, which is totally unknown to the 
majority of them. It might be suggested that what is not done 
by all might be done by a few for special reasons. This, how- 
ever, is not admissible in the case of our patients, because for 
several years they had lived in the asylum, and through informa- 
tion obtained both from their respective families and themselves we 
learnt in the most positive manner that they had never eaten maize. 

" !STor can the opponents of the maize theory, if there be still 
any, avail themselves of these five cases of mine to breathe new 
life into the inanition theory, because it will suffice that I point 
out that our patients had already been a long time in the asylum 
where the food has always been plentiful and of good quality, 
and that even before admission, though poor, had never suf- 
fered from starvation. On the other hand, since we are unable 
to ascribe the erythema to the use of alcohol on account of the 
time they had been in the asylum and because they had always 
been abstemious before admission, we are led to the conclusion 
that our patients are suffering from that form of chronic derma- 
titis which A. Brianchi, among others, believed to be due to the 
sun's rays, and which, indeed, is called pellagra or pseudo-pellagra 
of the insane." 

Professor Tambourini showed to Sambon and Lavinder a case 
in his ward which came from the mountain village, Rocca Priora, 



104 A TREATISE ON PELLAGRA 

in the Roman territory. This was the first case of pellagra from 
this place and maize could not be connected with its origin nor 
was there a history of alcohol or syphilis. The erythema had 
appeared two years previously and there was mental confusion, 
paresis, and rigidity of the trunk and limbs. He was a field 
laborer, and while his family ate polenta two or three times a 
week, he would never partake of it, always eating wheat bread; 
but the other members of his household remained well. It was a 
typical case of pellagra and the diagnosis w;i- concurred in by 
both Lavinder and Sambon, who had -ecu many eases of the 
disease. There were many more examples just as convincing as 
this one. 

Sambon quotes the following paragraphs from an address of 
Prof. G. Sanarelli, under-secretary of state for agriculture, at 
the 1909 Pellagra Congress: 

" The beneficial results derived from the application of the law 
of 1902 became evident so soon that already in 1905, less than 
three years after its passing, the pellagrins within the kingdom 
were reduced to barely 55,000, showing a decrease of over 17,000 
in the last six years. 

" Until we have a new pellagrin census to confirm the increas- 
ingly progressive reduction of this social sore, which, fortunately 
for our country, is gradually healing, we must from this very 
moment draw the most auspicious omens from the continuous and 
marked decline of the death rate due to pellagra within the last 
few years. 

" Indeed, whereas in the three years, 1887—89, the victims of 
pellagra throughout the whole kingdom were 10.2S4, in the next 
three years, 1900-02, they fell to 9,218; in the three years fol- 
lowing, 1903-05, they further declined to 7,367; and in the last 
three .years, 1906-1908, they have fallen to 4,619 only. 

" But there is something still more comforting. Whereas in 
1907, 4,950 new cases were notified, last year only 2,824 were 
reported. Whereas before the application of the present law, the 
yearly pellagra mortality constantly reached or even exceeded 



THEORIES OF ETIOLOGY 105 

the figure of 3,000, immediately after the year 1902 the number 
of deaths only just exceeded 2,000, in 1907 the deaths were 
1,63.5, and last year they were reduced to about 1,000. 

" Now, if on the basis of the last censuses of 1889 and 1905 
we can reckon that about 21,000 notified pellagrins corresponded 
to every thousand deaths from pellagra, we are bound to conclude 
that at present, within the whole kingdom, these unhappy beings 
do not exceed the number of 25,000. 

" Therefore, the prophylactic and curative work carried out 
within the last three years has further reduced the number of 
pellagrins by more than 50 per cent. 

" And this is a sure indication that the combined action of 
both the Government and the local bodies have attained decisively 
positive and greatly beneficial results." 

He further stated that if the law had been more vigorously 
enforced in all the forty-four affected provinces, the disease would 
have been wiped out. Sambon attempted to show that the law 
of 1902 did nothing at all in the direction claimed by Sanarelli. 
He said that the decline had already begun before the enactment 
of this law and that the law of 1902 did not go into effect until 
three years later, and then only for some of its least important 
provisions. He quotes an earlier statement of Sanarelli that went 
to show that notwithstanding the various reform movements there 
was no reduction in the number of cases. He then showed the 
obvious defects in all the prophylactic measures which the Italian 
Government had adopted. The reporting of cases, which by this 
law was compulsory, was absolutely farcical, as was the rule pro- 
hibiting the cultivation of the late varieties of maize, — that is, 
those varieties maturing late in the season, as forty-day and fifty- 
day corn. Until there is a more rigid supervision on the part of 
the Government it would seem hardly fair to draw deductions 
from the results. Certainly the decrease in pellagra in Italy can- 
not be attributed to these laws which have never been enforced. 

Sambon's idea that pellagra was a parasitic, insect-borne disease 
transmitted by an insect of a blood-sucking type had its inception 



106 A TREATISE ON PELLAGRA 

before he left London on his tour of investigation. The reasons 
for such a belief were as follows: 

(1) (a) The characteristic eruption and other symptoms of the 
disease may recur each spring for a number of years, notwith- 
standing the removal of patients from the endemic districts and 
the strict elimination of maize from their diet. This peculiar 
periodicity of symptoms can be explained only by the agency 
of a parasitic organism presenting definite alternating periods of 
latency and activity. Analogous periodicities are met with in 
other parasitic diseases — as, for example, in tertian fever, in 
which the periods of activity of the parasite (Plasmodium virax) 
recur each spring in correlation with the activity period of its 
anophelic definitive host. Xo toxic substance could account 
for it. 

(&) It presents peculiarities of distribution and seasonal inci- 
dence as in all parasitic diseases. 

(c) Its symptoms, course, duration, and morbid lesions are 
analogous to those of other parasitic diseases. 

(2) It is an insect-borne disease because: 
(a) It is not directly contagious. 

(&) Neither food nor drinking water can account for its 
peculiar epidemiology. 

(c) It is limited to certain rural districts only, towns and vil- 
lages almost invariably escaping. 

(d) It presents a definite and peculiar seasonal incidence — 
viz., spring and autumn. 

(e) It is practically restricted to only one class of people — 
viz., the field laborer, owing to greater exposure to infection. 

(3) It is conveyed by a Simulium because: 

(a) Simulium, so far as we know, appears to affect the same 
topographical conditions as pellagra. 

(&) In its imago stage it seems to present the same seasonal 
incidence. 

(c) It is found only in rural districts and, as a rule, does not 
enter towns, villages, or houses. 

(d) It explains most admirably the peculiar limitation of the 



THEORIES OF ETIOLOGY 107 

disease to agricultural laborers, a limitation which nothing else 
can explain in a satisfactory manner. 

(e) It has a wide geographical distribution, which seems to 
cover that of pellagra, although certainly exceeding it, in the same 
way that the distributional area of the anopheles exceeds that 
of malaria, and the range of Stegomyia calopus that of yellow 
fever. 

(/") It is known to cause severe epizootics in Europe and 
America. 

(g) Other similarly minute blood-sucking diptera such as 
Phlebotomus papatassi and Dilophus fehrilis are strongly sus- 
pected of being propagators of human diseases. 

Sambon found in Italy a peculiar attitude on the part of the 
medical profession, even those in the universities, towards pella- 
gra. There were many errors of diagnosis; such diseases as 
ankylostomiasis, dysentery, syphilis, and vitiligo being confused 
with it. In some instances the diagnosis was made on the gait, 
in others on the vertigo and debility. The value of the sym- 
metrical erythema as a pathognomonic sign was not appreciated, 
and its absence was not regarded as very important in arriving 
at the diagnosis. It was considered not an unusual thing for the 
skin lesion to be absent throughout the whole course of the 
disease. On the other hand a symmetrical erythema commonly 
observed was called by them " ethyl erythema," because it was 
attributed to alcohol. Sambon found that this so-called alcoholic 
affection was really pellagra occurring in the alcoholic individual. 
He also found that it was not an uncommon thing for the true 
pellagrous erythema to be overlooked by the physician. He con- 
cluded that the erythema was the earliest, most distinctive, and 
essential manifestation of the disease. This has been my experi- 
ence, and I have never seen a case of pellagra in which the ery- 
thema was absent throughout the whole course of the malady. As 
stated on a previous page, I did not find, as did Sambon, that 
it was limited to the agricultural population. From his report 
we see at once that this observer had a very thorough knowledge 
of the nature of the disease and, in fact, his description is one 



108 A TREATISE ON PELLAGRA 

of the best to be found in the English language. One could 
hardly view lightly any statement this man would make. He said : 

" After surveying several districts I became more or less familiar 
with the nature of the pellagra haunts, so much so that in Umbria, 
on visiting new districts, which could be viewed from the com- 
manding height of their inhabited center, usually perched on a 
high hill, I ventured to tell the local health officers whence I 
thought their pellagrins came from, and my guess was invariably 
right. 

" Both in northern and central Italy I found that the pellagra 
stations are, as a rule, in the narrower valleys of hilly and 
wooded country, trenched by swift-running streams infested with 
Simulium. This is the reason why pellagra is so common among 
the foothills of the Alps and Apennines, but the disease also 
spreads out into the plains, following the streams as far as the 
fly will reach, alternately extending and restricting its domain 
with the flows and ebbs of Simulium life. 

" That pellagra is especially prevalent about the lower slopes 
of mountainous regions was known long ago. Indeed, Pujati 
(about 1740) gave it the name k Alpine scurvy,' and Sartago 
(1791) proposed to call it ' mountain scurvy,' and Odoardi (1770) 
described it as a disease peculiar to the mountains and valleys of 
Belluno, expressing the belief that it would probably also be 
found in other mountainous countries. Strombio (1794) pointed 
out that it lurked among the hills of Brianza. And Cerri (1807) 
stated that pellagra is essentially a disease of the hills and lower 
mountains. 

" In all its European centers, whether in Italy, Portugal, 
Spain, France, Austria, Hungary, Croatia, Dalrnatia, Bosnia, 
Servia, Bulgaria, Turkey, Greece, Roumania, Bessarabia, Kher- 
son or Poland we find pellagra stationed at the base of the moun- 
tain ranges, along the streams which flow out of the mountain 
valleys into the subjacent plains. 

" So far as I know, prior to my papers on the etiology of 
pellagra, no causal connection was ever suspected by any one be- 



THEORIES OF ETIOLOGY 109 

tween pellagra and streams of running water, notwithstanding 
that numerous authors had mentioned the special prevalence of 
the disease along the banks of certain water courses. Odoardi 
(1776) pointed out that pellagra is very prevalent along the left 
bank of the Piave; Strombio (1794) noticed that it is common 
' among those who dwell along the River Olona '; Pagani (1806) 
stated that in Priuli the disease extends along the banks of the 
Tagliamento from S. Daniele to Valvasone ; Arrigoni Degli Oddi 
(1883) refers to the fact that near Padua the disease has been 
observed, as a rule, along the course of the canals ; Esposito 
(1902) reports a case from southern Italy, at S. Stefano, a village 
placed on the slope of a hill skirted by a rushing torrent, and not 
far from ISTocera Inferiore, where other cases have been observed. 
Even in other countries the disease has been noticed to prevail 
along the banks of rivers and brooks. Thus, in Hungary, Doctor 
Takacs (1889) observed it constantly along the banks of the 
River Szamos in the district called Szilagysag. Quite recently 
(May, 1910) Professor Alessandrini has confirmed my statement 
of a connection between stream and pellagra, but he repudiates 
the hypothesis of an insect carrier, and ascribes the disease to 
a nematode worm of undetermined genus, which he says he has 
found in the streams and is taken up in drinking the water thereof. 
His observations were carried out in Umbria, and more especially 
in the Districts of Gualdo, Tadino, and Assisi. ' In the former 
district,' he says, ' I was able to notice that the distribution 
of pellagra is typical and sharply limited by the course of two 
streams, the Rasina and the Sciola. These, together with the rail- 
way line, Roma-Ancona, divide the territory into two districts, 
— ■ one mountainous, consisting of the high Apennine Mountains, 
the other all hills. Whilst in the former there are no pellagrins, 
the latter, in all its fractions (Morano, Cova dell' Occo, Grello, 
Pastina, Badia, Pieve, San Pellegrino, Piaggie, Poggio Ercolano) 
is full of them, so much so that all the pellagrins of the District 
of Gualdo Tadino (254 people: 192 women, 62 men) belong 
to these fractions. The same may be said to be the case in Assisi, 
where the fractions most affected are those of the plain and hills.' 



110 A TREATISE ON PELLAGRA 

" The first pellagra district I had the opportunity of visiting 
this spring was that of Trescore Balneario, in the Province of 
Bergamo, where I went with Professor Balp, Drs. Siler, Perico, 
Baldini, and Mr. Amoruso. There, the very first pellagrins I 
was taken to see dwelt along the Tadone, a swift-running stream 
which flows into the River Cherio. On the slabs and boulders 
which form the bed of the Tadone we found numerous larvae 
and pupae of at least three different species of Simulium. Two 
of these, of which we reared adult specimens, were sent to Mr. 
Austen for determination and were found to be Simulium 
pubescens Macq., and S. omatum var. fasciatum Mg. 

" After that first observation, wherever I found endemic 
pellagra there also I found both stream and Simulium. 

" Professor Balp, to whom 1 had explained my theory, stated 
that his mind was quite open with regard to the etiology of 
pellagra, but that he knew of numerous cases of the disease in 
mountain districts far above any stream. I said those were the 
very districts I should like to visit so that I might at once dis- 
miss my theory if it failed to explain satisfactorily the distri- 
bution of the malady. Accordingly, Professor Balp took me to 
Clusone, a small historical town on the slope of a mountain, at 
648 meters above sea-level. To get to Clusone from Bergamo, 
one travels by train along the glorious valley of the Serio until 
one reaches a place called Ponte della Selva, then the road winds 
up the mountain through a forest of stately pines. Whilst driving 
up, I said to Professor Balp and Doctor Perico that, judging from 
the nature of the place, I should not expect to find any pellagra 
at Clusone. But Professor Balp took out of his pocket-book the 
official list and said there were no less than eighty-three cases 
notified. I have already stated that when we got to Clusone 
we only found a single imported case of many years' standing. 
At Clusone we partook of luncheon, and w T hen we were served 
the inevitable ' polenta ' some one jocosely asked the local phy- 
sician whether it could be eaten without fear of contracting 
pellagra. I then ventured to say that the pellagra we had not seen 
at Clusone would probably be found down by the Serio at Ponte 



THEORIES OF ETIOLOGY 111 

della Selva. Doctor Perico offered to go with me, and we started 
down the road that leads to Ponte Briolta, whilst the others 
followed DeVille, who went into the pine forest to shoot wood- 
cock. Doctor Perico and I reached the Serio at a place called 
Piario. The few houses which form the hamlet seemed deserted, 
all the good people of Piario were out in the fields with the ex- 
ception of an old goitrous female of facetious humor who could 
give us no information. However, in the following stream, we 
met a young woman carrying a child in her arms, and we found 
that the child had a typical pellagrous rash on hands and face, 
though the mother was quite unaware of the nature of the eruption, 
which she believed to be the redness of severe sunburn. This 
woman told us of a carpenter of Piario who was known to be a 
confirmed pellagrin, but we were unable to see him because, at the 
time, he was a long way off mending a roof. 

" The check at Clusone did not disconcert Professor Balp ; 
he owned that, with regard to that place, he had relied on local 
information, but he insisted that there were other places higher 
up in the mountains, such as Castione della Presolana, at 870 
meters above sea-level, where he had himself not only seen but 
even photographed numerous pellagrins. Therefore, on another 
day, we made an excursion to Castione, at the foot of the snow- 
clad Presolana, and there we certainly did find many cases of 
pellagra, but as already stated, those we examined proved to 
be imported cases. However, Castione has its stream of rushing 
water, the Torrent Borzo, in which Professor Balp was the first 
to find a few Simulium larvse. 

" At Padua, Professor Stefani and Doctor Randi, to whom I 
also explained my views on the etiology of pellagra, said they 
doubted whether my theory could hold good in their province, be- 
cause there were many cases of the disease in the neighborhood of 
the town of Padua, but no torrents or swift-running streams, and 
that the disease was prevalent among the Euganean Hills, a 
volcanic group noted for the scarcity of water. 

" The provincial medical officer, Doctor Randi, and Professor 
Stefani drove Doctor Siler, Mr. Amoruso, and myself to Chiesa- 



112 A TREATISE ON PELLAGRA 

nuova, where the local health officer, Doctor Carrer, showed us the 
locanda sanitaria, and then took us around to see the family 
Pavinato, with five pellagrin children, already mentioned, and an- 
other case of a child aged seven, belonging to a family of well-to-do 
farmers. As we drove along the dusty road which runs in a 
straight, staring white line along the perfectly flat country, and 
saw nothing but pools and ditches of stagnant water almost covered 
with Lemna or Spirogyra, Doctor Siler began to chaff me about my 
theory. Where was I going to find the howling torrent, the flying 
stream, and the aerated- water-loving midge ( Certainly, it was 
obvious that there could be no roaring mountain torrent in the level 
Paduan plain, but, perhaps, the pellagra cases notified in that dis- 
trict might prove to be imported cases, or there might be rapidly 
flowing irrigation canals that we had not yet seen, or, again, 
Simulium in the choice of its habitat might not always adhere quite 
strictly to the rules set out in the entomologist's text-book. At the 
locanda sanitaria of Chiesanuova the commensals we found gath- 
ered there were like the commensals of all locande sanitarie, a 
motley assemblage of poor, sickly creatures, several of whom pre- 
sented the signs of a pellagra infection of long standing, probably 
contracted many miles away. I did not trouble about them. With 
regard to the Pavinato children I was able to ascertain that they 
had contracted the disease many years ago, probably elsewhere. It 
would have been apparently reasonable, therefore, to dismiss this 
case as one of hereditary transmission, but I am very doubtful 
about this mode of transmission, and I chose to look upon it as 
a proof that pellagra is endemic, or at any rate it is capable of 
transmission in the District of Chiesanuova. 

"The day following I had arranged. to meet Doctors Lavinder 
and Blue, who were coming from Milan to see some typical cases 
of Italian pellagra ; I, therefore, instructed Mr. Amoruso to return 
very early next morning to Chiesanuova, examine the water courses 
of the district, whatever their nature, and endeavor to find me a 
test-tube full of Simulium larvae by noon, when I expected to 
reach Chiesanuova with the American colleagues. Pellagra ap- 
peared to be endemic in the district ; if this were so, then to 



THEORIES OF ETIOLOGY 113 

the best of my belief Simulium must be present ; to him the task 
of finding it. At the appointed time, on approaching Chiesanuova, 
I saw Amoruso in the distance waving a test-tube, and I knew 
that he had been successful. He did not find many larvse, but 
he discovered a number of pupse and empty pupse-cases in sluggish 
and almost stagnant water courses. The peasants who watched 
him collect the cocoons of the tiny aquatic silkworm told Mr. 
Amoruso that in early spring all the water courses run far more 
swiftly. 

" In all districts comprising both low, flat, or hilly, well- 
watered areas, and more or less massive mountainous areas, I 
invariably found pellagra to prevail in the former, and to be 
absent in the latter." 

Thus, at considerable length he details case after case to show 
that the two conditions, pellagra and swiftly flowing streams 
infested with the Simulium, went hand in hand. Where he found 
the Simulium he always found pellagra and the converse was 
equally true. He points out that the epidemiological picture is 
much like that of trypanosomiasis, Rocky Mountain fever, and 
malaria as well as other diseases transmitted by insects and having 
very definite habitats. Out of the endemic centers the sporadic 
cases were found to be in those who were in the habit of frequent- 
ing infected districts. He further shows that in the endemic 
centers the disease attacks all ages and sexes and even whole 
families. He mentions the case of two peasants who had lived 
by the Torrent jSTestore, but were compelled to abandon it be- 
cause of the pellagra. As soon as they took up their residence 
elsewhere the disease disappeared. Cases are cited where pella- 
grous parents having pellagrous children after leaving the " fly 
district " would have healthy non-pellagrous children born to 
them. 

Sambon emphasizes the definite areas of endemicity and states 
that these areas do not change from year to year. It is too soon 
to say with any degree of accuracy that this statement would hold 
true in the infected portions of the United States. Certainly, I 



114 A TREATISE ON PELLAGRA 

have seen a number of cases in one neighborhood and I have also 
seen six cases in one house. One of my patients was the wife 
of a man who had died during the year previous of pellagra. 
It cannot be said that these areas occur always out of the cities 
and towns. Such was Sambon's experience, as well as the ex- 
perience of practically all who have written on the subject. In 
North Carolina we see many cases in such cities as Durham, and 
we often hear of cases occurring in Atlanta. This fact does not 
weaken Sambon's theory in my opinion because of the fact that 
many, if not all, of the victims can be shown to have visited 
the country at some more or less remote period. The possibility 
of such an inaccuracy and such a point against Sambon's theory 
recalls to my mind the beautiful English Garden in Munich 
with the " Iser rolling rapidly " through it, and I wonder if, in 
the event of pellagra ever occurring in this fascinating Bavarian 
city, it would be a point against the Simulium theory. I recall 
the case of a miller who owned a mill for the grinding of corn 
into meal by water power. He developed pellagra, and the idea 
was that the disease owed its origin to the habit of eating raw the 
grains of corn during his work. It would be equally as fair 
and possibly more so to attribute the trouble to the Simulium- 
infested stream. 

It is a notable fact that such eminent pellagrologers as Babes 
of Roumania, whose work has previously been referred to, have 
left the maize theory to accept this of Sambon. Likewise, this 
view is upheld by Sir Patrick Manson in the last edition of his 
book and also by Castellani and Chalmers in their writing on 
tropical diseases. 

For my own part I feel confident that we are dealing with a 
parasitic disease, though I am not satisfied that the Simulium is 
the particular intermediate host in the transmission. Much more 
must be done before even Sambon himself would be willing to 
quietly accept this view. In the United States we are taught 
by no less an authority than L. O. Howard that this theory is not 
possible, for the reason that the Simulium habitat does not con- 
form to the endemic centers of the disease. However this mav 



THEORIES OF ETIOLOGY 115 

be, I was unable to secure any knowledge from Washington that 
helped to solve the question, so I proceeded to investigate for 
myself. I soon learned that the buffalo-fly was well known to all 
cattle people, and I also found that there was one specimen in the 
North Carolina Museum at Raleigh. Surely this one fly did not 
arise spontaneously so many miles away from the habitat in New 
York State, which is the only definite habitat I have been able to 
acquire any knowledge of from authorities. I would be unwilling 
to accept the information obtained from the country people re- 
garding this fly until it is further investigated. It is a fact that 
the habitat of pellagra in North Carolina is not along the sea 
coast where the streams are tidal and more or less sluggish, but 
in the Piedmont section where the towns are situated on rapidly 
flowing streams which are made use of in the various manufactur- 
ing industries for which this state is famous. In the high moun- 
tains I have been unable to find the disease except sporadically, 
and in the hospitals in Asheville only a small number of cases 
have been collected from the adjoining mountainous counties. 
In 1907 we saw a large number of cases in Wilmington, but 
recently in that city the disease has become very rare and all 
of my cases for the past three years have come from the interior 
counties. On reviewing the earlier cases in the light of Sambon's 
hypothesis, that is, from a geographical standpoint, I was im- 
pressed with the fact that a large number of those people, who 
had been affected with pellagra in this coast city, were new- 
comers. I hope to be able to prove that the others were exposed 
to infection during visits in the hill country. There are isolated 
cases where the disease has occurred on the very beach of the 
Atlantic Ocean, but in these cases I was able to find rapidly flowing 
brooks, which had a considerable fall in the last few hundred 
yards of their course before entering the sounds. It is not un- 
likely that the Simulium will be found to have a suitable abiding- 
place even this near the ocean. It has often been a problem to 
us why Onslow County in this same state was never infested 
with pellagra, as it has a relatively large number of poor whites 
and hookworm disease is very prevalent. The surrounding coun- 



THEORIES OF ETIOLOGY 117 

ties have suffered from pellagra much more. In fact, until quite 
recently no cases were discovered there, in spite of the fact that 
it is famous for its excellent medical profession, and every phy- 
sician in the county was familiar with the disease. This county 
lies on the Atlantic and is very low, with only tidal water, and 
no rapidly running streams. It is a notable fact that pellagra 
is more prevalent in those sections where there are to be found 
water mills. Can this be due to the fact that this water is the 
favorable breeding-place for the host % 

The work of S. J. Hunter, professor of entomology in the Uni- 
versity of Kansas, deserves especial mention and commendation. 1 
The first authentic cases of pellagra occurred in Kansas in July, 
1911, and the State Board of Health, through its secretary, who 
was Dean Crumbine of the University of Kansas, determined to 
have the sand-fly theory investigated. Consequently on August 
1 a survey of the streams in the vicinity of the cases was made. 
As the streams were muddy and high from recent rains the adult 
fly was sought first. The writer had had previously in the 
Mississippi valley between Keokuk and Fort Madison, Iowa, an 
opportunity to study the workings of the adult female, which is 
the biting sex, on horses, especially colts. The fly is so vicious 
that after warm rains it attacks the stock in such a manner 
as to actually denude the ears and throats and expose patches of 
raw flesh. On the date mentioned numerous specimens were col- 
lected from the ear of a brood mare and, when the streams had 
fallen, abundant larvse and pupae were found. Within four hun- 
dred yards of the home of the pellagrins was a small stream. 
Attached to the tree roots in this stream was found a large colony. 
The root produced a sufficient ripple in the water for the safe 
development of the eggs. The only species of the sand-fly found 
in Kansas was the Simulium vittatum. So far, the Simulium 
reptans has not been found on this continent, except in Greenland. 
Hunter's experiments consisted in allowing the Simulium vittatum 
to bite one of the pellagrins. Until October 12 he noted that 

1 Hunter, S. J., " The Sand-fly and Pellagra," Jour. Am. Med. Assoc, L VIII, 
pp. 547 and 548. 



118 A TREATISE ON PELLAGRA 

the fly would not bite, but from that date on they bit freely, 
drawing blood. By November 8 the male monkey which was 
bitten in turn by the fly which had previously bitten the pellagrin 
showed signs of inactivity and rapidly became decidedly ill, 
" crouched on the floor of the cage and was both unwilling and 
unable to ascend to his perch. He remained ill all day, getting 
worse, till late in the afternoon he became flaccid and motionless 
save for a high rate of respiration, ranging from 45 to 60 per 
minute. His temperature was 103.6° F., a little above normal. 
He appeared about the same the next morning, but improved a 
little during the day and continued the same until November 12, 
refusing all food, but drinking water freely." This work is still 
being carried out and one would be justified in expecting splendid 
returns from it. 

Grimm of Savannah has made an interesting study of the 
epidemiology of pellagra from the standpoint of topography. 1 
He found that in his series of sixteen cases studied that all of 
them lived within five hundred yards of a running stream; the 
majority lived within two hundred and fifty yards, and some 
actually on the very banks. These people lived in the valleys for 
economic reasons and consequently the streams were quite rapid. 
No work was done to determine the presence or absence of the 
Simulium group of biting flies. 

The cotton-seed products theory of AEizell was brought forward 
in 1911. 2 There hardly seems any occasion to discuss it at any 
length. It is not probable that the Spanish, French, or Italian 
peasantry nearly two hundred years ago were exposed to this- 
danger. As to the adulteration of olive oil with cotton-seed oil 
it will be seen that more peanut oil is introduced into France 
each year than cotton-seed oil. Peanut oil is much more often 
used to adulterate olive oil than the cotton-seed oil. It should be 
remembered that in Greece pellagra has never made any great 
inroads, according to the literature, but it is a well-known fact 

1 Grimm, R. M., "Pellagra: A Study in its Epidemiology." Lancet-Clinic, 
March 2, 1912. 

2 Mizell, in The Journal-Record of Medicine of Atlanta. 1911. 



THEORIES OF ETIOLOGY 119 

that these people eat olive oil on Wednesdays and Fridays, ac- 
cording to a rule of the Greek church ; during Advent and during 
Lent this oil takes the place of meat. There is no evidence in 
the United States that the consumption of cotton-seed oil has 
been associated with the appearance of pellagra. I heartily agree 
with the wise utterance of Zeller when he strikes a note of warn- 
ing against the condemnation of valuable food stuffs. If the 
use of maize and fat is taken away from the poor whites of the 
South what will be left for them to subsist on ? In my own prac- 
tice among these poor, unfortunate victims of pellagra I propose 
to add to their diet as much peanut oil, cotton-seed oil, and olive 
oil as their deranged digestive apparatus will stand. I have been 
accustomed to advise the use of cotton-seed oil among my tuber- 
cular patients when they were too poor to buy olive oil, and I 
have- yet to note any ill results from it. It has been contended 
that cotton-seed would kill hogs after one year's feeding and that 
the trouble lay in some toxic substance contained in the seed. 
It has been demonstrated by Mr. W. E. Worth of Wilmington, 
North Carolina, who is a large cotton-seed manufacturer, that 
hogs can be successfully fed cotton-seed without any result except 
the very best fattening returns. In certain experiments performed 
by him it was shown that the supposed cause of death is not 
toxicity, but the fact that the lint on the cotton-seeds is not 
digested but forms tough masses in the intestinal tract, which 
finally results in complete obstruction and death. When delinted 
seed was used there was no such ill result and the animals re- 
mained in the very best condition. 



CHAPTER III 

GENERAL CHARACTERISTICS OF THE DISEASE 

Pellagra is an endemic disease of unknown cause, occurring 
usually in temperate and subtropical countries, characterized by 
symmetrical skin lesions, chiefly of the exposed portions of the 
body, by gastrointestinal disturbances, and by changes in the ner- 
vous system. It is generally chronic in nature and terminates in 
recovery, insanity, or death. 

The disease attacks all ages and seems to be peculiarly free from 
any tendency to select a particular period of life. ~Ny youngest 
patient was 22 months and the oldest 75 years with all ages be- 
tween equally affected, except in infancy and childhood when the 
occurrence is said by most observers to be unusual. In the Peoria 
State Hospital a the following was the distribution of cases : 

From 20 to 29 years 4 cases 

30 to 39 " 18 cases 

40 to 49 " 2S cases 

50 to 59 " 29 cases 

60 to 69 " 16 cases 

70 to 79 " 3 cases 

80 to 89 " 2 cases 

Merk's table is of greater value for the reason that the above table 
was made from the inmates of an insane institution where there 
were no children and where the ages were not to be considered as 
representing the whole community. Merk's cases were of all ages 
and not from an institution whose inmates were of any special 
period of life. 

1 Bulletin of the Illinois State Board of Health, Vol. V, No. 7, p. 442. 



GENERAL CHARACTERISTICS OF THE DISEASE 



121 



'om 


to 


5 


" 5 


to 


15 


" 15 


to 


30 


" 30 


to 


40 


" 40 


to 


50 


" 50 


to 


60 


" 60 


to 


70 


ier 70 







Merh's Table of Ages 

years 46 

" 406 



cases or 0.9% 
cases or 8.3% 
715 cases or 14.7% 
919 cases or 19.0% 
1017 cases or 21.0% 
868 cases or 18.7% 
638 cases or 13.1% 
228 cases or 4.6% 



4836 



100.3% 




Fig. 5. — Professor Sambon and Umberto Pavinato, aged 3. 
pp. 53 and 74. By courtesy of Professor Sambon.) 



(Progress Report, 



It will be noted that the period of life between thirty and fifty 
years suffers most, but it will also be noted that no age is spared. 



122 A TREATISE OX PELLAGRA 

Christoferetti a reported five case- of pellagra. The ages ranged 
as follows: 17 months, 7 months, 40 days, 10 months, and 5 
months. 

As a rule children are not seriously affected, the malady often- 
times being overlooked and the child never reaching an institu- 
tion. I have seen only one fatal case in childhood; the patient 
was a negro girl of eleven years. In the first cases in Xorth Caro- 
lina, Bellamy 2 lost three cases in one family but at that time all 
cases were fatal. The majority of our cases were in barefoot chil- 
dren whom we ran down in our search for other cases, and while 
our experience with cases at this age was considerable, seldom 
was medical aid sought for them. Marie' 1 states that the age 
most affected is from 20 to 40 years bnt that children are no! 
exempt. 

The question of sex has always been counted of great importance 
in the study of pellagra. It is interesting to note the following 
table from the report of the Tennessee State Board of Health 
Pellagra Commission : 4 

Total Cases 316 

Male Whites 98 

Female Whites 200 

Male Colored 4 

Female Colored 14 

Lavinder found more cases among female negroes. This has not 
been my experience to any marked degree. It is usually considered 
that the female is peculiarly susceptible and the Tennessee report 
above would tend to bear out this idea. One writer, drawing con- 
clusions from a few cases, thought it was peculiarly a disease of 
men. It may be said that the influence of sex is trivial with a 
slight preponderance of females affected. 

1 Christoferetti, Dr. Leonello. in " Ein Beitrag zur Kenntnis von der Ent- 
wicklungdauer der Pellagra," von Dr. Ludwig Merk. 

2 Bellamy, R. H., Jour. Amer. Med. Assoc. 1909, Vol. LIII. 

3 Marie, "La Pellagra," translated by Lavinder and Babcoek. 1910. 

4 "Pellagra: A Report upon 316 Cases of this Disease by the Commission 
appointed by the Tennessee State Board of Health." Nashville, 1911. 



GENERAL CHARACTERISTICS OF THE DISEASE 123 

In the southern states the consideration of the relative number 
of cases in the two races is very interesting. Certainly the means 
of determining this fact are of very doubtful reliability for the 
reason that the physician who attends the negro usually has com- 
paratively few cases among the whites except in rural sections 
where there are usually no negro physicians. The institutions 
in this section are separate for the two races so that conditions 
in one might not be the same as conditions in another. It was 
noted in the Tennessee table that only eighteen cases were negroes, 
while there were two hundred and ninety-eight whites. My own 
experience has been that in North Carolina the number of negroes 
affected has been as small relatively as in the Tennessee report. 
Certainly the zeists cannot claim anything from this for the reason 
that maize forms a much larger element in the diet of the negro 
than in the white. I am inclined to think that the difference is 
due to the fact that, as Stiles has shown so often, the negro is 
not so susceptible to hookworm disease as the white, and, in 
fact, hookworm disease in the negro race is counted a rare 
condition. Pellagra shows a strong tendency to attach itself 
to a victim of any chronic disease whose resistance is lowered, 
and this is especially true of hookworm disease. A large number 
of the pellagrins in the southern states are also victims of uncina- 
riasis. It is also a fact that the negro in the South is usually 
better conditioned than the poor white. The reason for this is 
not apparent. 

Pellagra frequently attacks the victims of uncinariasis, as stated 
above, as well as the sufferers from malaria, tuberculosis, alcohol- 
ism, poor hygiene, poverty, pregnancy, and too frequent child 
bearing. The Tennessee report is again of value; it shows the 
following : 

Hookworm 10 Syphilis 6 

Tuberculosis 18 Thyroid disease 25 

Mental 4 Indigestion 4 

Age 8 Epilepsy 3 

Invalid „ 4 Alcoholism 2 

None 186 Other diseases 46 



124 A TREATISE ON PELLAGRA 

Sambon's x reference to this subject is so important that it is 
herewith reproduced m toto: 

" Associated infections and other debilitating conditions have 
a very marked influence in predisposing to the development of 
pellagra and in rendering its course more rapid and severe. 

" In quite a number of cases I found that the manifestations 
of pellagra had followed upon an attack of some antecedent disease 
such as enteric fever, malaria, dysentery, rheumatic fever, whoop- 
ing-cough, cardiac disease, or some other debilitating affection. 
In women, pregnancy and parturition seem to be very common 
predisposing causes. In one patient traumatism appeared to have 
determined the outbreak of the disease. Many other diseases are 
similarly influenced by antecedent or concomitant maladies. It is 
well known that a latent tuberculosis may be suddenly awakened 
into activity by an attack of enteric fever or measles, that in 
children suffering from whooping-cough the rubeola eruption is 
remarkable for its intensity, that pulmonary tuberculosis, pneu- 
monia, erysipelas, run a rapid course in diabetics, whose glucose- 
steeped tissues seem to attract every kind of pathogenic organism 
just as their ' honey urine ' attracts ants. 

" With regard to the part played by malaria, Doctor Severi, 
health officer of Torgiano, Perugia, gave me a very interesting ex- 
ample. He said that in 1880 the Chiagio, a tributary of the Tiber, 
overflowed its banks and gave rise to a large swamp, which was al- 
lowed to stand for over eight years. The swamp brought about the 
appearance of a prodigious number of toads, which on certain days 
literally covered the highroad to Bettona, and the diligence was 
obliged to drive over them, crushing thousands of their puffed-out 
bodies. At the same time, swarms of mosquitoes arose, and 
malaria broke out and lasted until 1888, when the course of the 
Chiagio was deviated and the swamp dried. The malaria epidemic 
was immediately followed by an unprecedented increase in the 
prevalence and severity of pellagra. 

1 Sambon, L. W., " Progress Report on the Investigation of Pellagra." Lon- 
don Jour, of Trop. Med., 1910. 



GENERAL CHARACTERISTICS OF THE DISEASE 125 

" At the Pellagra Congress held at Bologna in 1902, Professor 
Devoto stated that in Mantua in March, 1901, the Po gave rise 
to serious inundations, which were followed by numerous cases 
of malaria and, consequently, owing to the lowered resistance, by 
a notable recrudescence of pellagra. 

" In most of the pellagra districts visited by me, malaria is 
practically unknown, therefore, only in one case have I been able 
to observe the co-existence of the two diseases — a well-marked 
pellagrous rash in a young man who presented a fever of decided 
tertian type and Plasmodium vivax in his blood. 

" Ankylostomiasis is another affection undoubtedly of impor- 
tance as a predisposing factor. It is true that ankylostoma eggs 
are not infrequently found in the feces of patients presenting only 
a slight pellagrous rash, but I am convinced that ankylostomiasis, 
and especially a severe form of the infection, must play a very 
decided part in the development of pellagra, as it certainly does in 
kala-azar, beri-beri, and other diseases." 

Sambon's experience in Italy has certainly been ours in I^orth 
Carolina and probably throughout the southern states, wherever 
careful study of the cases has been made. One of the first cases 
seen by me, which is represented in Figures 2, 3, and 4, was one of 
a severe malarial infection. The malaria was thought to be the 
cause of the skin lesions and reported thus : " A Mixed Infection 
with Tertian and Quartan Malaria Occurring in a Patient with 
Symmetrical Gangrene." * The occurrence of this combination 
of quartan and tertian parasites had never before been noted in this 
country and was thought to explain the curious condition with 
which none of us were familiar. This is only one of a large num- 
ber of instances of this occurrence of malaria either coincidentally 
or as a predisposing cause of pellagra. It is very probable that the 
occurrence of large numbers of cases of pellagra in certain of the 
mill towns of the South is favored by the presence of hookworm 
disease. Many of my own cases presented this infection and in 
some cases it was very severe. There are many other parasitic dis- 

1 Wood, E. J., Jour. Amer. Med. Assoc, Dec. 7, 1907, XLIX. 



126 A TREATISE ON PELLAGRA 

eases which in the same manner predispose the patient to pellagra. 
Figures 6, 7, and 8 and Chart II are from a patient who, during 
her stay in the James Walker Memorial Hospital under my care, 
passed over one hundred round worms. William Allen x of Char- 
lotte, North Carolina, found monads in the stools of five out of 
seven pellagrins and concluded that these patients were peculiarly 
liable to intestinal parasitic infection. Four out of five cases 
studied by him showed the presence of small ameboid organisms in 
the stools. He found no larger amebse present and was uncertain 
whether or not these organisms belonged to the amebae family, or 
were monads in the prefusion stage, or were ameboid cells from other 
sources. He considered that there was great likelihood of mistak- 
ing amebiasis for pellagra because of the presence in both diseases 
of diarrhea and stomatitis. In such cases the occurrence of a con- 
siderable eosinophilia would point to intestinal parasitic infection. 
The part played by heredity in pellagra has been considered else- 
where and is a matter of importance, but the disease is too recent 
in the United States for us to draw any first-hand deductions, and 
until the next generation we must rely on the opinion of European 
observers entirely. Albera (1781) and Odoardi (1776) con- 
sidered the disease hereditary and Strombio, the elder (1794), 
considered it so because so many pellagrins were the children of 
pellagrins. But, as the children of pellagrins are not all attacked 
in every instance, he concluded that it was both inherited and ac- 
quired. Sambon 2 quotes Zecchinelli (1818) in this connection: 

"No one doubts any longer that pellagra is a hereditary disease 
since it may be clearly seen affecting whole families, more espe- 
cially within those districts in which it has longest prevailed, as in 
the districts of Cesana, Limana, Arsie. Quero, and Alano (in the 
province of Belluno). So far, however, hereditary transmission 
has been observed to occur solely amongst the lower classes, which 
are everywhere extremely poor. Hitherto, hereditary pellagra has 

1 Allen, W., " Amoebae in the Stools of Pellagrins." Trans. Nat. Cong, on Pel- 
lagra, 1909. 

2 Sambon, L. W., Progress Report, etc. 



GENERAL CHARACTERISTICS OF THE DISEASE 127 

not been observed in prosperous families which have remained 
almost entirely free from the disease even though placed in the 
very midst of the most severely affected populations. If at times 
a pellagrin has been seen in families not really poor, besides being 
a very rare case, it was always the only case in the family. For 
pellagra to be transmitted by heredity it is necessary, even amongst 
the poorest families, that one of the parents be in the last stages 
of the disease. And for the disease to be transmitted to newborn 
infants, it is necessary, indeed indispensable, that the pellagrin 
parent be the mother, either pregnant or suckling." 

Soler (1791), Facheris (1804), and Marzari (1815) opposed 
the theory of heredity, but one of them, at least, admitted the pre- 
disposing factor of heredity. Lombroso (1892) 1 mentioned two 
forms of hereditary pellagra. One was mild and the other severe. 
The first, he said, was a true " pellagra-sine-pellagra," while the 
second appeared in the second year and was characterized by des- 
quamation, pyrosis, epigastric pain, voracity, uncertain gait, fear- 
fulness, diarrhea, a form of jaundice similar to that seen in ma- 
laria, and deficient and retarded development. Later all the mani- 
festations of the disease were recorded and there was noted marked 
resistance to treatment. In some cases he claimed to find mal- 
formations of the skull, extraordinary brachycephaly, or dolicho- 
cephaly, retreating forehead, mal-position of the external ears, 
asymmetry of the face, and anomolies of the genital organs. He 
also thought the disease could be transmitted by atavism to the 
grandchildren. 

Agostini, according to Sambon, says : 

"... Whilst in the majority of children born of pellagrin par- 
ents, the heredity manifests itself by a reduction of the vital ener- 
gies, a congenital psychophysical weakness, a development always 
imperfect and irregular, and a peculiar predisposition to respond 
to the influence of the pathogenic agent pertaining to the sur- 
roundings in which they live, viz., the maize poison ; in a certain 
number of patients the degenerative factor having been accumu- 

1 Lombroso, C, " Die Lehre von der Pellagra." Berlin, 1898. 



128 A TREATISE ON PELLAGRA 

lated in their procreators, brings about the gravest syndrome of 
somatophysical degeneration such as dystrophic cretinoid, and 
myxedematous infantilism." 

Christoferetti reported a case of pellagra in a fourteen-months- 
old child. The child was brought to the clinic on October 1 by its 
mother, who reported that the sickness began in July. This was 
the fifth child and the father had had pellagra for five years. The 
mother had been feeble for one year and had always required sev- 
eral months to recover from childbirth. Although a pellagrin she 
had nursed the child for three months, but since the fourth month 
the nursings had been supplemented with corn meal cooked with 
milk and water. At the end of the first year the child began to 
fail. The condition on admittance was that of typical pellagra. 
Two of this child's brothers are healthy, but a sister of eight years 
is hydrocephalic and has had pellagra for three years. With the 
removal of corn from the dietary improvement was immediate. 
The observer closed his report with the statement that hereditary 
pellagra is not scientifically recognized. This case satisfied Christo- 
feretti that corn and not heredity was at fault, and he did not think 
that any proof of the heredity of the disease could be produced. 1 

Sambon's view seems quite reasonable. He says : 

" The belief that pellagra is a hereditary disease is untenable now 
that we know that diseases are not hereditary in the scientific sense 
of the word ' hereditary.' There is no hereditary small-pox, no 
hereditary tuberculosis, no hereditary syphilis, and likewise there 
can be no hereditary pellagra. "Whether pellagra may be acquired 
in utero by means of placental or amniotic infection is a different 
matter. Several authors have reported the disease in ' new-born ' 
children, but no one has ever described a case in which the infant 
was born with the characteristic signs of the disease upon it. 
I have no reason to doubt that pellagra may be acquired in utero, 
but I have never seen a congenital case myself, nor have I ever 

1 Christoferetti, L., " Pellagra in fruehester Kindheit. Gleichzeitig ein Bei- 
trag zur Kenntnis von der Entwicklungsdauer der Pellagra." Wden. klin. 
Wochr., 1906. 



GENERAL CHARACTERISTICS OF THE DISEASE 129 

heard of one. According to my experience, antenatal pellagra, if 
it does occur, must be exceedingly rare. Within the endemic 
areas, pellagra affects entire families and, as might be expected, 
the disease is very common in young children and infants, but in 
such places the children are exposed to the very same influences 
which engendered the disease in their parents, blood-collaterals, and 
ancestors. In non-endemic areas, such as Castione della Presolana, 
in the province of Bergamo, notwithstanding the presence of nu- 
merous pellagrins, I was unable to find a single case of the disease 
among the younger children, whether their parents were pellagrins 
or not. I examined with special care the children of families in 
which both parents were pellagrins and had contracted the disease 
before the birth of the children, but I was unable to detect any 
sign of the disease in the offspring. Indeed, these children dif- 
fered in no way from the children of non-pellagrin jDarents living 
in the same locality. 

" Both physicians and peasants told me of pellagrins whose elder 
children, born in a pellagrous district, were also pellagrins, whilst 
the youngest, born after removal to a healthy locality, were entirely 
free from the disease. On the other hand, it has frequently hap- 
pened that in a family the four, five, or more healthy children born 
in a pellagra-free district acquire the disease all at the same time 
on taking up residence in a pellagrous locality. I have already 
mentioned the example of the family Pavinato, in which five 
healthy children simultaneously contracted pellagra on removing 
to Frasinelle in the province of Rovigno. Another well-attested 
fact is that children sometimes become pellagrous first, their par- 
ents afterwards. Thus the two sons of Giovanni Ferrario, of Cas- 
tione della Presolana, contracted the disease in the neighboring 
Province of Brescia several years before their father, for the simple 
reason that they both went to work in an endemic locality several 
years before their father. Although children are very frequently 
affected, I have often seen patients upwards of eighty years of age 
who had been pellagrins for two or three years only. Thus Placido 
Ferrari, of Castione, eighty-one years of age, contracted pellagra 
three years ago in the province of Brescia soon after taking up field 



130 A TREATISE ON PELLAGRA 

work, which he had never done before. He has always fed on 
cheese and polenta. His family consists of eight members, but he 
is the only pellagrin." 

It has been well noted that the degeneracy found in pellagrous 
districts may be accounted for by other diseases as malaria, hook- 
worm disease, and many other similar chronic diseases. 

No phase of the study of pellagra in the southern states has been 
so interesting as the consideration of the class of people affected 
and the occupations. In this respect the American experience has 
been somewhat unique and furnishes rather an interesting de- 
parture from the European idea. We often hear the expression 
of pellagra and poverty being interchangeable terms. In the south- 
ern states the extreme poverty of southern Europe is practically 
unknown. There is no class in this section which at all corresponds 
to the peasant class of Italy. The negro is usually well fed and 
comfortably clothed. His condition is probably better than that 
of the poor white. It is rather difficult to understand why the con- 
ditions among the poor whites should be more deplorable than 
among the negroes in the same locality. The labor situation in the 
South to-day is such that any man white or black can always find 
work at good wages. The cotton crop in Xorth Carolina and South 
Carolina this season was partly left unpicked because pickers could 
not be had. Any man in the South to-day who will work cannot 
starve, but another important factor enters at this point : the white 
man is often unable to work from physical infirmity. It will ap- 
pear to the reader that the explanation which I am about to give is 
improbable, but it can be borne out by no less authority than 
Charles Wardell Stiles as well as many other workers of the Rocke- 
feller Commission for the Eradication of Hookworm Disease. The 
negro has been shown to be much less susceptible to hookworm in- 
fection than the white. Hookworm disease is a problem of great 
magnitude in the same sections where pellagra is prevailing. There 
can be no doubt that it is one of the greatest predisposing factors 
in the production of pellagra. But even in some of the most un- 
hygienic mills of the South where hookworm disease is prevalent as 



GENERAL CHARACTERISTICS OF THE DISEASE 131 

well as pellagra the economic conditions are far superior to those of 
the class in Italy which suffers so terribly from this great scourge. 

My case records show that the disease is not confined to the 
poorer element of our population. I have seen pellagra in society 
women, in teachers, in professional men, in bankers, in wealthy 
merchants, and in every other walk of life from the least to the 
greatest. It has always been held in Europe that the disease is 
almost exclusively limited to the field laborer, and from the earliest 
writings we learn that Erapolli, Gherardini, and Odoardi as well as 
many others considered it a disease entirely of the rural sections 
and that cities were veritable places of refuge from it. Sambon 
found that the majority of cases examined by him were in field 
laborers, but even this class was not affected except in the endemic 
centers. He further claimed that healthy mechanics and workers 
in other classes of labor than agriculture would become pellagrous 
when they became tillers of the soil. He found the disease occa- 
sionally in coachmen-, fishermen, and priests as well as in shep- 
herds, carpenters, masons, and shoemakers, but explained this by 
the fact that at certain seasons of the year these people would go 
into the fields to help out in the rush. While pellagra is known 
to occur quite frequently among the farming people the fact re- 
mains that this class is not so universally affected as in Europe, 
xlgain, it is interesting to note that in America the disease is often 
found in the cities. Many cases have been reported from Atlanta, 
Mobile, New Orleans, Charlotte, Columbia, and other cities. Quite 
notable is the occurrence of a large number of cases in the thrifty 
city of Durham, North Carolina, one. of the wealthiest cities of its 
size in the United States. It has never been carefully enough 
studied to determine just how much time these victims of the cities 
spend in the country each year. It is a common custom in the 
South as well as in other sections to leave the cities with the ap- 
proach of warm summer weather and to seek cooler places in the 
country. 

The table of the Tennessee Commission is quite valuable in 
regard to the distribution of the disease among the various 
occupations. 



132 A TREATISE ON PELLAGRA 

Housewives 141 School Boys 12 

None 30 Washerwomen 1 

Miners 9 Paupers 1 

Laborers 29 Cooks 1 

School Girls 22 Miscellaneous 38 

Farmers 32 

Pellagra is subject to very definite seasonal variations. This 
is one of its most characteristic features which has been noted from 
the earliest description and which is valuable from the standpoint 
both of treatment and diagnosis. These variations are usually con- 
sidered recurrences and a recurrence is dated from the appearance 
of the skin lesions. The time of the year at which this event occurs 
is subject to great variation, depending on geographical position and 
the character of the particular season. An early season will bring 
about the earlier appearance of pellagra while a cold spring will 
retard the outbreak. I have had cases to appear in every month 
from March to October but the greater number of cases in North 
Carolina make their appearance in April and May. In Italy the 
spring recurrence of the erythema usually occurs in March or 
April, but it may appear as early as February. The last cases in 
Italy are said to occur in June. The autumn recurrences occur in 
September and. October. It often happens that a patient who has 
had the erythema in the spring will have a recurrence again in the 
autumn. In Egypt the outbreak may occur as early as January. 
All through the summer months pellagra may be studied in the 
southern states. As above stated there never occurs a month from 
March to October without a number of cases. Lavinder and Bab- 
cock are authority for the statement that during the months of May 
and June the number of cases is greatest and they are more severe. 1 
In addition to these seasonal recurrences there also occurs very 
definite exacerbations of the erythema which do not occur in all 
cases nor at any regular interval. This peculiar manifestation will 
be mentioned later at some length ; suffice it to say that this condi- 
tion must not be confused with a recurrence. It may be distin- 

1 Marie's " La Pellagra," translation by Lavinder and Babeoek. 



GENERAL CHARACTERISTICS OF THE DISEASE 133 

guished by the peculiar lamellated appearance suggesting the layers 
of a shell. 

The question of the contagiousness of pellagra is naturally a 
matter of the greatest importance. The question is constantly asked 
us in the South if pellagrins can be admitted with perfect safety 
to the wards of the general hospitals. In many places there are 
restrictions forbidding such cases. No phase of this question is 
of so great interest to the public as this. From the earliest writ- 
ings on the subject much has been said in this connection. Strom- 
bio, the elder, stoutly denied the statement of some of his prede- 
cessors who claimed that the disease was contagious. His logical 
reasoning did much to dispel the idea of communicability. Since 
his time little has been said on this subject for the reason that a 
disease caused by the eating of maize could hardly be considered 
under any other head than that of grain intoxication. Roussel 
considered that the problem had been definitely settled for all time 
and he emphatically stated that pellagra was not contagious. In 
certain sections of the United States, since the appearance of pel- 
lagra, steps have been taken for the establishment of measures for 
the isolation and quarantine of the disease but this has by no means 
been general. Lavinder recently wrote : 

" If communicable at all pellagra certainly does not seem to be so 
in any very direct way from one individual to another. Evidence 
is not lacking that pellagra is possibly a disease of place or locality, 
somewhat after the apparent nature of beri-beri. This, however, 
does not necessarily imply anything as to its transmissibility." * 

Sambon's view regarding this question of the contagiousness of 
pellagra is summed up by him in his denial of this possibility thus : 

" (1) The narrow limitation of pellagra in certain centers, often 
very small, while there is free communication between their inhab- 
itants and the neighboring population; (2) The almost exclusive 

1 Lavinder, C. H., "Pellagra: A Precis" (Revised Edition), Public Health 
Bulletin, No. 48. 



134 A TREATISE OX PELLAGRA 

limitation of the disease to field laborers; (3) The absolute im- 
munity of urban populations, notwithstanding frequent intercourse 
with numerous pellagrins from the country; (4) The frequent 
limitation of the disease to only one member of large families living 
under the most insanitary conditions and sharing the same bed; 
(5) The absolute immunity of doctors, nurses, and inmates of 
hospitals and asylums in which pellagrins are admitted; (0) The 
non-transmission of the disease from wet nurse to child by means 
of lactation; (7) The failure of all attempts to reproduce the 
disease by means of the inoculation of the ichorous matter from 
the skin lesions or the blood and saliva of pellagrins made by 
Gherardini (1780), Buniva (1805), De Rolandis (1824), and 
others." 1 

Among the writers x who believed that pellagra was transmissible 
were Van-der-IIeuvell (1787), Videmar (1790), Titius (1792), 
Zecchinelli (1818), Hamean (1829), Frank (1842), Botto 
(1846), and others, as well as a number of American observers of 
recent times. It is the general opinion in Italy that the disease 
is not contagious and this view is borne out by the fact that the 
pellagrins live crowded together within the unaffected areas in 
miserable huts, but the disease is not transmitted. In recent years 
the more accurate laboratory work along these lines tends only to 
substantiate this view. The work of Anderson and also of Lavinder 
in their attempts to produce the disease experimentally in the 
rhesus monkey were not conclusive. Recently many autopsies have 
been performed on victims of the disease in this country without a 
single case of transmission, and this was the experience of the Euro- 
pean observers. All of these facts seem to justify the conclusion 
that pellagra is not transmissible in the generally accepted sense of 
that term, and any efforts at isolation seem not only unnecessary 
but unjust. The fact remains, however, that the question cannot be 
intelligently disposed of until the etiology is definitely determined. 
In the report of the Tennessee Commission it will be found that 
among the cases reported there were one hundred and seven ex- 
posures and one hundred and nine cases without such a history. I 

1 Sambon. L. W., Progress Report, p. 90. 



GENERAL CHARACTERISTICS OF THE DISEASE 135 

have many records in my case book of interesting illustrations 
which bring up this question of transmissibility. In one house I 
have seen six cases of pellagra occurring simultaneously. In an- 
other house were four cases. A man died under my care with pel- 
lagra, and one year later I was called on to treat his wife for 
the same disease. A woman died from pellagra and in a year 
her brother met the same fate. If the cause is damaged food it 
would be a simple matter to explain these occurrences on the ground 
of a common exposure. If Sambon's hypothesis is proven to be a 
truth, then we must explain it on the same ground on which we 
explain the occurrence of malaria. Until the cause is known and 
understood it will not be possible to answer the question as to 
whether this is a mere coincidence or whether there is an element 
of transmissibility direct or indirect to be considered. There can 
be no doubt of the correctness of the statement made both by Sam- 
bon and Lavinder that pellagra is a disease found in certain very 
definite areas. This accords with the idea of Sambon, who ex- 
plains this occurrence on the ground of an intermediate host. 

The length of the incubation period of pellagra cannot be defi- 
nitely determined and the views expressed differ according to the 
number of expressions for no two seem to agree. That it is as long 
as some suppose can be disproved by the fact that it occurs in 
infants only a few months old as will be seen from another refer- 
ence. Sandwith said in, this connection: 

" It is difficult to fix any incubation period because the onset of 
the disease is so insidious. But it is perhaps worth referring again 
to the fact that the maize crop in lower Egypt is harvested in No- 
vember or December and that the bulk of the patients seem to begin 
their eruption in January. It is unlikely that the November crop 
could become so poisoned by the fungus as to produce a skin erup- 
tion in January after, presumably, an intervening period of pre- 
monitory symptoms. I think we must, therefore, assume that the 
eruption is the result of poisoning from the previous year's crop or, 
in other words, that the incubation is perhaps from nine to twelve 
months' duration." 



136 



A TREATISE ON PELLAGRA 



Merk states that maize alone causes the erythema and that his 
observation teaches him that from seven to nine months must elapse 
before the appearance of the erythema. Sambon thinks that the 
incubation period is about three weeks. His basis for this belief 
is the fact that an infant of four or five months born in Xovember 
or December may have the disease. As this is several months be- 
fore the seasonal recurrence only three months are left to be ac- 
counted for, and he subtracts six weeks from this because the child 
is as old as that before taken to the field. This would place the 
incubation period at from three to six weeks. Sambon's view is 
subject to all the criticism of the views of his predecessors and, 
possibly, to much more. Seheube speaks of a prodromal stage 
which might be confused with the period of incubation. Certain 
it is that there is such a prodromal stage which may be, as Seheube 
says, as much as several years. It is highly probable that during 
this period, if sought for diligently, there could be found symp- 
toms which would be definite enough to stamp them in the light 
of subsequent developments, not as true prodromal symptoms, but 
as symptoms of the developed disease. 

There are several types of pellagra and the number will vary 
according to the individual observer. The chief types, however, 
are the ordinary chronic pellagra which in America we sometimes 
find ourselves calling " the Italian form," which means merely 
that it is the usual type seen in a country where the disease has 
long occurred and where it has assumed a definite course. This 
chronic type is subject to many variations. In one case the skin 
lesion may be trivial while in another universal ; in one case the 
gastric symptoms may predominate, while in another the chief 
symptom is the diarrhea ; or, again, there may be an absence of all 
gastrointestinal manifestations. 

Typhoid pellagra, or typhus pellagrosus, is a term used to desig- 
nate a condition which is thus given by Belmondo, 1 according to 
Lavinder : 



1 Belmondo, " Le alterazioni anat. del midollo spinale nella pellasrra, etc." 
Riv. Sper. di Freniat., Reggio-Emilia. 1889 and 1890, XV and XVI, quoted by 
Lavinder in Public Health Bulletin, No. 48. 



GENERAL CHARACTERISTICS OF THE DISEASE 137 

" It is rare that typhoid pellagra develops suddenly, for, as a rule, 
the ordinary -symptoms of pellagra show a characteristic intensity ; 
the enteritis and the nervous phenomena (neurasthenia and pa- 
resis), as well as the general weakness, assume an unwonted im- 
portance, and even on the psychic side there are clouding of con- 
sciousness, depressed tone, and a tendency to suicide. 

" Most of the cases are poorly nourished and at times much 
emaciated ; however, there are others in which the panniculus adi- 
posus is abundant and the general development of the muscles re- 
mains almost normal. There is often almost absolute unconscious- 
ness, at times verbigeration or visual hallucinations of a terrifying 
nature. 

" The entire musculature is in a very pronounced state of tonic 
contraction, and there is marked rigidity evident on making passive 
movements of the extremities. In these manifestations the reflex 
rigidity increases and generally the passive movements ultimately 
become impossible. Often the patient makes spontaneous, inco- 
ordinate movements, especially with the hands and arms, from time 
to time. In these movements, apparently intentional, there is 
shown frequently a tremor of the upper extremities, with wide 
oscillations and a certain grade of ataxia. The speech is drawling, 
the voice trembling and often nasal. 

" The face has a rigid and contracted appearance; however, at 
intervals the mimic muscles, principally those of the mouth, are 
agitated by tremors which spread from one muscular fasciculus 
to another and reach even distant muscles. 

" The lower extremities are habitually in forced extension, the 
feet in plantar flexion. The exaggeration of the reflexes increases 
up to the last hour of life, the knee jerks being especially exagger- 
ated. Even a definite ankle clonus is not rare. Under a light per- 
cussion on the tendon of the quadriceps there is often a spasmodic 
reaction of the leg, accompanied by convulsive movements of the 
whole body. At times, together with the plantar clonus, there is 
a paradoxical contraction of the extensors of the foot, and hyperes- 
thesia to tactile stimuli so marked that a breath of air or a ray of 
light may provoke motor disorders or tonic convulsions." 



138 A TREATISE ON PELLAGRA 

As Lavinder says, the name " typhoid pellagra " is most unfor- 
tunate as there is no feature of the condition which even suggests 
typhoid fever, but is an acute explosion which is peculiar to pel- 
lagra and occurs as an incident in the chronic course of the disease. 
There is said to occur a varying amount of fever which at times 
may be quite high. Death usually follows after from two to six 
weeks. The accompanying temperature charts show a condition 
which, while it occurred in pellagra, could hardly be attributed to 
it. In one case (Chart I) the rises of temperature were undoubt- 
edly clue to a coincidental malarial infection as the malarial or- 
ganisms were unusually abundant and were of the remarkable 
combination of tertian and quartan types. In the oilier case (Chart 
11) no such specific cause could be found excepl the presence of a 
large number of round worms, but the extent of the skin lesion 
which was of the moist variety was so event that there resulted an 
enormous absorbing surface with a resulting mixed infection. Tem- 
perature rise in this case was as much to be expected as in any 
superficial burn which was allowed to become infected. Typhoid 
pellagra is usually considered an acute exacerbation of the usual 
chronic condition — a terminal phase. The description of the 
European authorities emphasizes the acute nervous symptoms and 
in such states independent of pellagra the rises of temperature as 
recorded would not be difficult to explain. I have repeatedly seen 
this condition. It was well illustrated in the case of a white 
woman, aged 39 years, who had the typical skin lesions, including 
the erythema of the face, neck, and arms. Her whole body was in 
a constant state of tonic contraction. She refused all food, but if 
it was left within reach she would eat it when left alone. She was 
possessed with the insane idea that she was not lawfully married 
to her husband but was living in a state of fornication and adul- 
tery. Her statements were so plausible that we accepted them and 
were amazed later to learn of the error. She became so violent 
that the restraining sheet became a necessity. Her clothing as well 
as the bed w r ere covered with blood and crusts which resulted from 
her incessant movements about the bed. There was a slight rise 
of temperature. Death resulted after three weeks. This was the 



GENERAL CHARACTERISTICS OF THE DISEASE 139 

third year of the disease and complied accurately with Belmondo's 
conception of typhoid pellagra. In the case illustrated in Figs. 6, 
7, and 8 and in the temperature chart (Chart I) is seen another 




Fig. 6. 



An Eleven-year-old Negbo Girl with Symmetrical, Moist Lesions 
oi' Hands, Forearms, Face, and Neck. 



state which in the United States has been confused with typhoid 
pellagra. In this case the patient had the moist type of the ery- 
thema on the hands, forearms, and whole of the face and neck 
including the external ears. The chart shows the temperature 



140 



A TREATISE ON PELLAGRA 



which I have mentioned above and attributed to a mixed infection 
by way of the skin. This patient died before there was time for 
the development of any definite nervous changes. This class of 




Fig. 7. — Same Patient as Rephesented in Figs. 6 and 8, Showing the Posterior 
Aspect of a Casal's Collar. 



cases should be designated as fulminating or acute and should be 
carefully distinguished from the terminal state of the chronic 
type of the disease. 

Lombroso described seven types of the disease which* are men- 



GENERAL CHARACTERISTICS OF THE DISEASE 141 

tioned merely as a matter of interest but cannot be commended as 
a classification for the student : 

( 1 ) Insane cases. 

(2) Those who seek the water for relief from the intolerable 
burning. 

(3) Cases with a tendency to fall backwards. 




Fig. 8. — Same Patient as Figs. 6 and 7. Note Secretion between the Fingers. 

(4) Cases in which the patient assumes a bent-over attitude. 

(5) Cases with vertigo or fainting spells. 

(6) Cases with voracious appetites. 

(7) Cases with the skin lesions. 



These seven forms of the disease were reallv recognized in the 



Venetian pellagrins, 
cock is interesting: 



The following note by Lavinder and Bab- 



" Sandwith says he has often seen all these varieties in Cairo, 
though the second and third are the most rare and the fourth is 



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GENERAL CHARACTERISTICS OF THE DISEASE 143 

not common. We, too, have seen all kinds in this country, though 
the second and third are rare in our experience, and the fifth, while 
fairly common, is not of the severity usually described in Italy. 
Furthermore, Babes and Sion, in commenting on this subject, say: 
' It is true that a popular proverb speaks of different kinds of pel- 
lagra, but they do not stand the test of scientific criticism.' " x 

Mention will be made later of that type of the disease known 
as " pellagra-sine-pellagra," which signifies pellagra without skin 
lesions. It seems unwise at this time in the United States for stu- 
dents of this disease to accept such a possibility as a settled scien- 
tific fact. After we have acquired more experience with the disease 
possibly we may become sufficiently trained to recognize such a 
condition, but at the present, for the sake of conservatism, it would 
be unwise to make such a diagnosis. Strombio was the first to rec- 
ognize such a condition. It was seriously questioned by Roussel, 
who thought that it was merely a stage of the disease in which there 
was an absence of the skin lesions, but that these lesions had either 
been present and had disappeared or would appear later in the 
course of the disease. Lombroso recognized pellagra-sine-pellagra 
as a congenital form of the disease only. In all of the cases of 
pellagra-sine-pellagra which have come under my attention it has 
been possible by a careful investigation to find on the elbows or the 
forearms or even on the face faint traces of an old erythema which 
is usually manifested by the remnants of the hyperkeratotic border 
which is often quite distinct and is always a valuable symptom. 
Many patients manifest only a very slight erythema which may be 
readily overlooked even by the patient himself. It must be remem- 
bered that the order of the appearance of the symptoms of pellagra 
may be greatly modified and in some instances the erythema will 
not appear until very late in the course of the disease. Before the 
appearance of this pathognomonic symptom the condition is often 
called pellagra-sine-pellagra. 

Roussel divided pellagra into three great heads. The first was 
pellagra of the first degree, which he called spasmodic pellagra, 

1 Lavinder and Babcock's Translation of " La Pellagra," by A. Marie, p. 182. 



144 A TREATISE ON PELLAGRA 

and which corresponded to the intermittent form of Strombio. 
This head was subdivided into beginning pellagra and developed 
pellagra. The second was the paralytic form or the remittent of 
Strombio. The third head was pellagrous cachexia, and under 
this head were two sub-heads : one with eruption which Strombio 
called the continuous form, and the other without eruption. This 
latter was merely a resulting cachexia. 

The clinical manifestations of pellagra are usually divided into 
four stages : ( 1 ) the pre-erythematous stage, which is usually con- 
sidered a prodromal stage; (2) the stage of erythema, in which 
there occur, in addition to the erythema, various digestive dis- 
turbances and some central and peripheral nervous disturb- 
ances; (3) the stage of severe cerebro-spinal disturbances and 
psychic phenomena; (4) the cachectic stage, which is usually 
terminal. 

The first or prodromal stage usually begins about Christinas and 
is characterized by very indefinite symptoms such as anorexia, or 
voracious appetite, pain, and sensation of distension in the epi- 
gastric region, usually diarrhea, though the reverse condition of 
constipation may occur or the two conditions may alternate. Some- 
times there is insatiable thirst or, on the other hand, there may 
occur an aversion for water. The tongue is thickly coated and later 
its epithelium is lost. Roussel considered sensations of dryness 
and burning in the mouth and heat in the stomach to be the first 
symptom of the disease. Even in this early stage of the disease 
there occur certain nervous symptoms which usually first manifest 
themselves with headache of the occipital type, pain in the neck and 
back, hyperesthesias, dizziness, and muscular weakness, especially 
in the lower extremities. Vertigo, in this stage, is a common symp- 
tom which is much emphasized in the Italian works, but in America 
it occupies a much less prominent position among the symptoms. 
Added to these symptoms we often see the typical globus hysterica, 
formication, uncertainty of motion, increased psychic irritability, 
ill-temper, and disinclination to work due to marked mental weak- 
ness. There is invariably found at this time a varying degree of 
neurasthenia. This prodromal stage may last only a few weeks 



GENERAL CHARACTERISTICS OF THE DISEASE 145 

or it may be prolonged into several years. Theodori found it to 
he four weeks between the appearance of the first prodromal symp- 
toms and the erythema. Schenbe found it a varying period sub- 
ject to remarkable flexibility and was disposed to consider it much 
longer than usually accepted because he said that the prodromal 
symptoms were not recognized by the patient in giving a history 
as connected with the subsequently developing pellagra. Gregor 
thought that when neurasthenic symptoms lasted for several years 
without obvious cause pellagra should be suspected. Roussel con- 
sidered loss of appetite and gastric disturbances to be complications, 
but dryness of the esophagus, dysphagia, and pyrosis to be the first 
pellagrous symptoms. Roussel also regarded great hunger, vomit- 
ing, cardialgia, and diarrhea as nervous symptoms. It was noted 
by Babes that often preceding the erythema there was a peculiar 
redness of the lips and tongue, Lavinder and Rabcock noted a 
peculiar injection of the papilla; of the tongue, which were often 
pigmented. In the white race it was of an intense crimson and in 
the negro dark or black. They found it more frequently in' the 
negro and to it attributed the so-called " stippled tongue." In 
my own cases the changes in the tongue and mouth almost always 
preceded the appearance of the erythema of the exposed portions of 
the body, but this is not an unvarying rule as the stomatitis may 
be entirely absent or may appear some time after the appearance of 
the skin symptoms. It is a very characteristic symptom and is 
seldom absent though its time of occurrence may be very irregular. 
The condition of the mouth and tongue will be dealt with later at 
greater length. Here it is sufficient to say that there is general 
redness of the buccal mucosa and at times vesicles and ulcers may 
be present. Coincident with the appearance of the mouth symp- 
toms or soon after there appears the erythema which gave the name 
to the disease and which is usually accounted the most important 
symptom. All authorities are not of the opinion that this is the 
most important symptom. Sandwith thought it the least important 
and that it always received an undue amount of attention. In 
the United States, at least, until we become more familiar with this 
strange malady, which is certainly new to us, it would be unwise to 



146 A TREATISE ON PELLAGRA 

attempt the practice of making such a diagnosis without this 
valuable aid. In my opinion the erythema of pellagra should be 
regarded as pathognomonic and the diagnosis should never be jus- 
tified without it or a history of its past occurrence. I have before 
me as I write a patient who had the digestive disturbances, includ- 
ing the stomatitis with profuse salivation for two months before tbe 
appearance of the erythema. The time' of the appearance of the 
skin manifestations is as variable as the time of appearance of the 
mouth symptoms. There will be found later in this work the rec- 
ord of a case in which the first outbreak of the erythema occurred 
after the victim had become insane and after all other symptoms 
had become well fixed. The erythema appears in the spring after 
the weather has become warm, following the prodrome which is 
usually described as beginning at Christmas time. Exceptionally 
the first outbreak of the skin lesion occurs in the fall or winter. 
A recurrence of an erythema which had appeared in the preceding 
spring occurs not infrequently in the fall, but it is very unusual 
for an initial outbreak to occur in the latter season. The distinc- 
tive features of this erythema briefly mentioned are symmetry, 
location on exposed portions of the body, pigmentation and exfolia- 
tion. The symmetry is very definite and involves not only sym- 
metry of location but also of shape and size. It will be later shown 
in more detail just how exact this symmetry is. A skin lesion 
which does not occur on the exposed portions of the skin, or is not 
accompanied by such a lesion of the exposed portions must not be 
considered pellagrous, for the selection of this location is a definite 
peculiarity of the disease. The first appearance of this erythema 
strongly suggests simple sun-burn and for the first few days cannot 
be distinguished from it. In addition to the redness there. is often 
a certain amount of swelling. Following this there occurs exfolia- 
tion of the skin, which usually proceeds from the center to the 
periphery, leaving a border of brownish pigmentation which is the 
last remnant of the skin condition. This is spoken of as the hyper- 
keratotic border and is a valuable sign, especially in the examina- 
tion of a supposed case of pellagra-sine-pellagra. In America two 
types of skin lesion are recognized : the wet and the dry. They will 



GENERAL CHARACTERISTICS OF THE DISEASE 147 

be described at length on another page. The most common location 
of the pellagrous lesion is the backs of the hands. Following this, 
the lesion occurs on the face, the neck, the feet, and much more 
infrequently on the unexposed portions of the body as the perianal 
and perineal regions, the back, the scrotum, and the thighs. At the 
height of the attack nervous symptoms are commonly found to have 
already developed. The most usual symptom of this class is in- 
crease of the reflexes, though there is often a decided lessening of 
the reflexes depending, however, on the portion of the spinal cord 
affected by the degenerative processes. It has been repeatedly 
noted in the southern states that definite changes in the nervous 
system do not occur so often as in the European cases. This can 
probably be accounted for by the fact that in the former location 
pellagra has not yet entirely assumed the chronic and less severe 
type as seen in Italy and the patients have been dying before there 
was time for a definite impression to be made on the nervous tissue. 
It is no uncommon thing to find an entire absence of changes in 
the nervous system in such cases. 

The period occupied by these symptoms is usually from three 
to four months. The skin often remains for some time darker in 
color and sometimes rough and dry. Finally every vestige of the 
affection seems to have disappeared and many physicians with a 
limited experience in this disease assume that the treatment insti- 
tuted by them has been successful and establish unjust claims for 
certain drugs as a result. But the next spring brings about a repe- 
tition of all the symptoms mentioned. This repetition occurs 
usually each succeeding spring and with each recurrence the sever- 
ity of the symptoms is increased and a more indelible impress is 
left especially on the nervous system. I have known cases in which 
one whole year elapsed without a symptom of the disease only to 
see a reappearance with the next spring. For this reason alone it is 
wise to require two years without symptoms before counting a 
case recovered. 

The next stage of the disease is characterized by the appear- 
ance of severe cerebro-spinal disturbances. Subjectively the pa- 
tient complains of numerous parasthesias among which are itching 



148 A TREATISE ON PELLAGRA 

of the backs of the hands and occasionally of the feet, burning in 
the epigastrium, scapular region, the feet, the hands, and the arms. 
This burning is said to cause the tendency for the sufferers to 
plunge into the water. This weird performance has never oc- 
curred in our experience though it is mentioned by a number of 
the Italian pellagrologers. These patients often complain of formi- 
cation, sensations of cold, especially in the lower extremities, of 
globus hysterica, of pain in the neck and the back. Headache of 
a dull character is often a constant symptom. Tinnitus aurium is 
a very frequent complaint. Probably the most constant complaint 
is vertigo. It occurs very often in the American cases, but is not 
so pronounced as it seems to be in Italy, judging from the litera- 
ture. Among the more unusual sensations complained of is that 
of a full uterus. 

Objectively the psychical symptoms are very prominent in this 
stage of the disease. The usual character is that of melancholia. 
In milder cases there is an interference with thought, slo\vnc>< of 
ideas, mild irritable depression, and an aversion to any form of 
activity (Tuczek). The patient often manifests a great anxiety 
because of past sins which are found to be entirely imaginary or 
greatly magnified. There is often the firm conviction of the un- 
pardonable sin. Delusions of grandeur never occur in uncompli- 
cated pellagra at any time. Always the mental attitude is one of 
profound depression or persecution. The patient will often refuse 
food to the point of starvation. This is not due to an inability to 
take food occasioned by the stomatitis which occurs earlier in the 
disease, but is purely a mental disturbance. Some writers describe 
a definite suicidal tendency. In our series there was not -a single 
suicide nor were we able to detect any such attempt. Tuczek did 
not find any tendency for such patients to become dangerous. 
"While our patients are usually very docile and too weak to be 
dangerous if they so desired, I have seen an attempt on the part 
of a woman victim to kill a whole household with an axe. Tuczek 
mentions the occurrence of a circular form of insanity composed 
of melancholia and mania. This is not unusual in the insane in- 
stitutions of the South. He also states that he never observed 



GENERAL CHARACTERISTICS OF THE DISEASE 149 

frank paranoia as did some other observers, but he did see a fatal 
termination in dementia paralytica. 

Certain motor disturbances have been described. Weakness of 
the muscles, especially of the lower extremities, is sometimes 
found. Owing to circumscribed paresis of the flexors the extremi- 
ties may be found in the semi-flexed position. Spasms and painful 
cramps sometimes occur. Paroxysmal painful tonic contractures 
in the lower extremities strongly suggesting tetany. Contractures 
of both lower and upper extremities in the semi-flexed position 
may occur. The decrease of muscle power may progress to partial 
paralysis. 

Tuczek 1 found the gait paralytic, occasionally paralytic-spastic, 
but never ataxic. Static ataxia occurs according to him occa- 
sionally and incoordination of motion, rarely in the upper ex- 
tremity, lie speaks of this condition having been described as 
intention tremor. In addition to tremor of the upper extremity 
tremor of the head and tongue have been described. 

Definite epileptiform attacks with loss of consciousness have 
been observed in rare instances. More commonly the attack simu- 
lated cortical epilepsy. In one of my earlier cases the patient died 
in an epileptiform convulsion after having had three yearly re- 
currences of the disease. 2 

In this stage the skin reflex as a rule is normal. The pharyn- 
geal reflex is often decreased. The tendon reflexes usually show 
various deviations from normal. They may be normal, increased 
even to the point of intense clonic contraction, or, less frequently, 
decreased. The tendon reflexes in the upper extremity may be in- 
creased and in the lower decreased or vice versa. Again, the reflex 
on one side may be decreased and on the other increased. 

The third stage, or the fourth stage if the prodromal period is 
counted as the first, is the stage of cachexia. It manifests itself 
with increasing marasmus, atrophy of the subcutaneous fat and 
muscles, and an inability to resist intercurrent diseases. Weak- 

1 Tuczek, F., " Klin. u. Anat. Studien ueber die Pellagra." 

2 Wood. E. J., "The Appearance of Pellagra in the United States." Jour. 
Amer. Med. Assoc, LIII, p. 274. 



150 A TREATISE ON PELLAGRA 

ness is so great that the patient is usually bedridden. Diarrhea 
is usually very severe and there is incontinence of both bowel and 
bladder. Death results often from a weakened heart muscle. 
Sometimes death is due to tuberculosis, and it is a well-recognized 
fact that pellagrins are peculiarly susceptible to this disease. 
Edema and effusions into the serous cavities often occur just be- 
fore death. It is in this period of the disease that the condition 
previously mentioned as typhoid pellagra supervenes. All the 
previously mentioned nervous symptoms at this time are exagger- 
ated. Speech is tremulous or drawling; there is marked tremor: 
the lower extremities are in a state of marked extension and the 
feet in plantar flexion; the head may be drawn backwards from 
contraction of the neck muscles, and occasionally it is raised up 
and moved from side to side in a convulsive manner. 

The division of the course of pellagra into stages is purely arbi- 
trary, and there cannot be drawn lines even as definite as in lues. 
It has already been shown that there is great flexibility in the 
order of the appearance of symptoms, and in one case frequently 
referred to in this work it would appear that what has been arbi- 
trarily referred to as the third stage really appeared at the time 
when the first stage would ordinarily be expected. This patient 
manifested definite mental symptoms many months before the in- 
testinal and erythematous symptoms. 

The blood changes in pellagra are important for many reasons, 
but more especially because they help to fix the place for the disease 
in medicine. Hitherto, pellagra has been accounted a grain intoxi- 
cation belonging to the ergot group. A study of the blood picture 
will be the greatest argument against such a conclusion. The fol- 
lowing blood report was made from a case of a girl of fourteen 
years brought to London by Sambon. 1 It was a typical case of 
pellagra. 

Red cells 4,850,000 

White cells 8.400 

Haemoglobin 95% 

1 Sambon, L. W., Progress Report. 



GENERAL CHARACTERISTICS OF THE DISEASE 151 

Differential leucocyte count: 

Polymorphonuclears 56.0% 

Large mononuclears 4.0% 

Lymphocytes = 37.6% 500 counted. 

Eosinophiles 0.4% 

Transitionals 2.0% 

Mast cells 0.0% 

100 

Further notes of this case were recorded thus : 

" The shape and size of the red cells were good. ~No parasites of 
any kind whatever were noted in the blood. In the differential 
count it will be noted that the lymphocytes (by that meaning small 
lymphocytes) are relatively increased. 

" This latter condition, a relative increase of the lymphocytes, 
was further borne out by a series of fifteen differentia] counts 
(500 leucocytes in each case) from different cases, the blood of 
which was brought by Doctor Sambon from Italy. In most of 
these this was present, and where it was absent there was generally 
something to account for it, such as a polymorphonuclear leucocy- 
tosis due to sepsis or relative increase of the eosinophiles, in all 
probability due to ankylostomiasis. 

-' The large mononuclear cells (by this meaning the type of cells 
usually seen in cases of malaria) were normal or diminished, cer- 
tainly never increased. The cases where eosinophilia was present 
all came from an area where ankylostomiasis was prevalent, and 
this in all probability accounted for it. 

" The changes found, then, in differential counts of the leuco- 
cytes in pellagra cases may be summed up as follows : In the ma- 
jority of cases a relative increase of lymphocytes is present ; there 
is no change in the large mononuclear percentage. 

" ISTo parasites of any kind were found in any of the speci- 
mens of blood examined, this bearing out the work of others. 
Special attention was directed to the possible presence of 
spirochaetes, a modified Indian ink method and other stains 



152 A TREATISE ON PELLAGRA 

being used; but the results were uniformly negative. Xothing 
of the nature of trypanosomes or other protozoal parasites was 
ever seen. 

" In several thick films of dry blood the hemoglobin was washed 
out, and the film was stained for filaria. The results again were 
negative. 

" There would seem, therefore, to be little to be gained from the 
examination of the blood in pellagra, but the failure to find any 
definite microscopical parasite does not, of course, exclude some 
ultra-microscopical germ as possibly being the cause of the disease 
(compare yellow fever, dengue, etc.)." 1 

Fratini, 2 Fiorini and Gavini, 3 and Masini 4 found a definite 
eosinophilia. The last-mentioned observer stated that the eosino- 
philia occurred in cycles corresponding to the increase or decrease 
of the pellagrous toxemia, and he thought it might prove a valu- 
able aid to early diagnosis. My own experience is that all instances 
of eosinophilia may be accounted for in some other way than by the 
pellagra. It is so frequent an occurrence for the disease to be com- 
plicated by intestinal parasitism, and as the two diseases occur in 
the same latitude it is not unreasonable to attribute this blood con- 
dition to another cause than pellagra. Drewry called my attention 
to the increase of the mononuclear elements of the blood, but at 
the time I was inclined to regard this increase as due to intercur- 
rent tuberculosis, which occurred in a number of his cases. My 
own study of the blood did not impress me with the unusual in- 
crease of these elements. In one of the earlier cases there was a 
remarkable malarial condition and blood slides were made every 
three hours for a number of days, but the findings, except for the 
presence of tertian and quartan parasites, were not at all remark- 

1 Sambon, L. W.. Progress Report, 1910. p. 107. 

• Fratini, G., " II reperto ematologico nei pellagrosi." Ric. pella, ItaL, Vol. 
VII, 1907. Quoted by Lavinder, Trans. Nat. Pel. Cong., 1909. 

3 Fiorini, M., and Gavini. G., " Contrib. alio studio della formula emoleuco- 
citaria nei pellagrosi." Riv. erit. di clin. med., 1905, quoted by Lavinder Trans. 
Nat. Pel. Cong., 1909. 

* Masini, M. U., " II tasso della cellule eosinophile," etc., Gior. di psichiat. 
Clin, e tech. Manic, Ferraria, 1900, quoted by Lavinder Trans. Nat. Pel. Cong.. 
1909. 



GENERAL CHARACTERISTICS OF THE DISEASE 153 

able. The following table of Daniels and ISTewham l is especially 
interesting in this connection : 



No. per c. mm. 



Poly- 
morpho- 
nuclear. 
Per cent. 



Lympho- 
cytes. 
Per cent. 



Large 
mono- 
nuclear. 
Per cent. 



Eosino- 

philes. 

Per cent. 



Pneumonia. Great increase up to 
60,000 

Sepsis. Increase up to 30,000 or 
40,000 

Liver abscess. Increase varies, 
often slight, 12,000 to 20,000 . 

Typhoid. Slight increase at most . 

Malta fever. Slight increase at 
most 

Relapsing fever. Great increase up 
to 50,000 

Malaria. No increase; decrease 
during pyrexia 

Trypanosomiasis. No increase . . 

Kala-azar. Marked increase, 1,000 
to 3,000 

Ankylostomiasis. Usually in- 
creased, especially in early 
cases 

Beri-beri. Slight increase, 11,000 
to 14,000 

Pellagra. 7,000 to 9,000 .... 



85 to 95 

75 to 90 

75 to 85 
50 to 65 

50 to 65 

75 to 90 

45 to 65 
50 to 65 

50 to 60 

66 to 70 

24 to 49 
50 to 60 



15 

15 to 25 

15 to 25 
25 to 40 

25 to 40 

10 to 20 

15 to 25 
20 to 30 

25 to 35 

10 to 20 

30 to 68 
32 to 42 



5 

5 to 10 

5 to 10 
5 to 15 

5 to 15 

5 to 10 

15 to 30 
15 to 20 

15 to 20 

5 to 10 

1 to 12 
3 to 6 



It is rather remarkable that the reduction in hemoglobin in pel- 
lagra should be relatively so trivial. With such a degree of 
cachexia one would expect a much more decided decrease. The 
following table of Lavinder is of interest : 2 

1 See Daniels and Newman's work on " Laboratory Methods in Tropical 
Medicine." 

2 Lavinder, C. H., " Hematology of Pellagra," Nat. Pel. Cong., 1909. 





'A 

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GENERAL CHARACTERISTICS OF THE DISEASE 155 

Even more noteworthy is the comparatively normal number of red 
blood corpuscles. This is found in both the table of Lavinder and 
that of the Illinois State Board of Health which is here given : x 









Blood. 




a 




Blood. 


■H 


£ 3 






d 


m fi- 


fi'3 

CD O 




6 










525 


»"S 


0"S 






£ 


ll 


Ow 






H 

CD 

< 


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CD 




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CD 


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CO 

< 




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■6 

CD 


o 


s 


w 


is 


Pi 


o 


« 


w 


£ 


« 


1 . . 










37 . . 


164 


40 


15,000 


1,500,000 


2 






103 


55 


16,030 


2,500,000 


38 . . 


176 








3 






138 


85 


9,200 


4,250,000 


39 . . 


118 


85 


8,000 


4,600,000 


4 






180 


83 


6,400 


3,750,000 


40 . . 




90 


25,000 


3,500,000 


5 






205 


85 


14,000 


7,000,000 


41 . . 


126 


85 


16,000 


3,500,000 


6 






132 


90 


10,000 


3,500,000 


42 . . 


164 








7 














43 . . 


175 


90 


14,000 


4,400,000 


8 






154 


75 


11,000 


3,750,000 


44 . . 


152 


85 


9,000 


3,250,000 


9 








70 


9,000 


2,350,000 


45 . 




80 


15,200 


3,700,000 


10 






170 


85 


6,400 


4,500,000 


43 . . 


155 


85 


10,000 


3,750,000 


11 






150 


70 


10,000 


3,900,000 


47 . . 


154 


85 


12,400 


4,250,000 


12 






134 


80 


11,000 


4,890,000 


48 . . 




95 


6,000 


4,300,000 


13 






138 


85 


12,000 


4,720,000 


49 . . 


140 


85 


7,600 


4,500,000 


14 






130 


60 


8,200 


5,200,000 


50 . . 


190 


85 


16,000 


3,000,000 


15 






162 


95 


12,000 


4,700,000 


51 . . 


140 


89 


6,600 


3,600,000 


16 






115 


90 


20,000 


4,500,000 


52 . . 


120 


85 


8,000 


4,000,000 


17 








95 


9,000 


4,250,000 


53 . . 


162 


80 


12,000 


3,500,000 


18 






132 


80 


8,500 


3,000,000 


54 . . 




80 


7,500 


3,600,000 


19 






158 


90 


11,000 


4,350,000 


55 . . 


152 


90 


7,000 


3,800,000 


20 






152 








56 . . 




89 


9,000 


4,800,000 


21 






134 








57 . . 


165 


80 


12,000 


4,000,000 


22 






123 


90 


14,000 


4,250,000 


58 . . 


170 


85 


10,000 


3,000,000 


23 






220 


80 


8,000 


4,000,000 


59 . . 


138 


75 


10,000 


3,500,000 


24 






196 


90 


6,000 


3,750,000 


60 . . 


105 


76 


3,600 


3,220,000 


25 








85 


10,000 ' 


3,900,000 


61 . . 


190 


95 


6.000 


4,700,000 


26 






107 


83 


9,600 


4,200,000 


62 . . 


170 


80 


8,600 


4,936,000 


27 






174 


75 


10,600 


3,000,000 


63 . . 


126 


80 


8,000 


3,800,000 


2S 






150 


80 


6,000 


4,500,000 


64 . . 


122 


55 


7,200 


1,800,000 


29 






164 


75 


16,000 


4,700,000 


65 . . 


134 


83 


6,000 


3,700,000 


30 






153 


50 


5,000 


3,250,000 


66 . . 


146 


85 


8,000 


3,750,000 


31 






184 


100 


10,000 


4,250,000 


67 . . 










32 






186 


85 


8,000 


3,600,000 


68 . . 


135 


90 


10,000 


5,000,000 


33 






132 








69 . . 


180 


90 


19,400 


5,240,000 


34 






135 


90 


4,600 


4,000,000 


70 . . 


195 








35 






176 


85 


10,000 


3,000,000 


71 . . 


160 


55 


5,000 


3,100,000 


36 






135 


75 


12,000 


3,700,000 


72 . . 


140 


85 


9,800 


4,500,000 



1 Monthly Bulletin of the Illinois State Board of Health, Oct., 1909, pp. 472 
and 473. 



156 



A TREATISE ON PELLAGRA 



Q 



73 . 

74 . 

75 . 

76 . 

77 . 

78 . 

79 . 

80 . 

81 . 

82 . 

83 . 

84 . 

85 . 

86 . 



(- 




Bl 


3^-> 


fl3 














ft El 

*2 


s a 


ci 






5 


ID 


is 



145 


65 


8,000 


160 


85 


9,200 


146 






120 


85 


8,000 


125 


90 


8,000 




90 


3,009 


140 


90 


8,000 


185 






105 


80 


4,503 


160 






100 


87 


5,099 


140 


80 


6,099 



3,750,000 
2,900,000 

3,7.50,000 

3,000,009 
3,509,000 
4,509,003 



3,700,099 



4,859,0)9 
3,750,009 



87 



90 

!tl 
92 
93 
94 
95 
96 
97 
98 
99 
190 



as 

gs 

5 



180 
134 
140 
125 
145 
182 
130 
115 
180 
108 
148 
120 
138 
230 



85 

ss 
78 
85 

85 
90 

90 

60 
90 



Blood. 



8,000 3,250,000 

11,000 4,700,000 

8,000 3,900,000 

10,000 3,900,000 



10,000 3,750,000 
30,000 5,350,000 

16,000 3,500,000 



4,000 3,000,000 
9,000 4,500,000 



There was found such a constancy in the normal proportions of the 
various blood elements that early in my study blood counts were 
abandoned. 

The following interesting' notes on one hundred pellagrins were 
made regarding changes in the urine (Marie) : In 76 cases it 
was slightly acid; in 14 cases it was neutral; in 10 cases it was 
alkaline. The urine was more often alkaline in severe cases and 
paralytics and the aged. In younger patients who suffered from 
cataleptiform or epileptiform attacks Caldarini observed the same 
condition of the urine. The latter observer in 33 cases found 
21 per cent of the specimens strongly acid, 57 per cent slightly 
acid, 12 per cent neutral, and 9 per cent alkaline. He 
found the specific gravity below normal ranging from 1005 
to 1010. Various reports regarding the amount of urine 
secreted in pellagra have been made. Some observers found 
even at the approach of death there was no decrease in the 
amount, while others find a decided decrease. Again, some ob- 
servers find in a large percentage of their cases a trace of albumen ; 
in the work of others there is a notable absence. Ardor urina? is 



GENERAL CHARACTERISTICS OF THE DISEASE 157 

a frequent complaint of pellagrins. It is claimed by Marie that in 
such cases there is also an increase in density and some dysuria, 
and, further, he claims that in spite of good nutrition there is a 
diminution of urea, of the phosphates, and of the chlorides. 

Indicanuria is a very common and oftentimes constant accom- 
paniment of pellagra. It was found to occur frequently in the 
earlier days of the study of the disease in this country. It was 
found by J. J. Watson in South Carolina in a large percentage of 
examinations. The same experience is reported by the Illinois 
report on pellagra. It is probable that this very constant presence 
of indican can be accounted for by the processes occurring in the 
intestinal tract which have resulted from the changes brought about 
by the disease. 

Eleanora B. Saunders made a careful study of the obstetric and 
gynecologic features of 21 cases under her care. 1 She shows that 
17 per cent of pregnant pellagrins abort; that pregnancy will often 
precipitate an attack of pellagra. It has been mentioned that pel- 
lagrins recover very slowly after childbirth and are often unable 
to nurse their infants. Vaginitis and vulvo-vaginitis are common 
occurrences in female pellagrins and have occurred frequently in 
my cases. Menstrual disturbances are very frequent and are sub- 
ject to many variations. As Saunders mentions multiparous pel- 
lagrins are subject to menorrhagia, which often suggests carci- 
noma. I have also noted this condition in nullipara and have seen 
the condition disappear promptly after arsenic treatment had 
brought about a general amelioration of symptoms. She found 
amenorrhea in 50 per cent and dysuria in 57 per cent. Leucorrhea 
is a very common and very persistent complaint. Marie attributed 
to this disease the large number of stillbirths among the Egyp- 
tian Arabs. Saunders emphasizes the importance of refraining 
from needless surgical procedure in pellagra. I have in mind a 
woman in good circumstances who developed pellagra in the Johns 
Hopkins Hospital after a gynecologic procedure and, on the other 
hand, I recall one of my earlier cases in which the diagnosis was 
not made at the time, who was treated surgically in the same 

1 Saunders, E. B., Trans. Nat. Pel. Cong., 1909. 



158 A TREATISE ON PELLAGRA 

hospital by Howard A. Kelly with a splendid effect on the pellagra. 
This latter patient has never suffered a recurrence. 

Eye changes have not been frequent in ray experience. A num- 
ber of my cases have been watched for eye changes by my colleague, 
J. G. Murphy, but nothing of note has been found. This care in 
ophthalmoscopic examination was incited by the fact that the use 
of atoxyl has been thought to bring about serious eye changes. My 
cases are almost invariably treated with this drug but never without 
a careful consideration of the possibility of this danger. The fol- 
lowing report on the eye in pellagra is taken from Lavinder and 
Babcock's edition of Marie's work : 

" Remarkable peculiarities are found in the eyes of the pella- 
grous; a falling of the superciliary fold is very frequent in severe 
cases — even unilateral ptosis is not rare. Inequalities of the 
pupils are very important and dilatation in the right eye is 
very frequent. In many cases is found also a marked unilateral 
injection of the conjunctiva. These are observations which remind 
one of general paresis, and show, along with other manifestations, 
how frequently the lesions of the nervous system may be unilateral, 
especially lesions of the sympathetic system. 

" Very often also (74 cases) mydriasis of the two sides is found. 
Myosis is more rare and when found is more usual in the aged. 
Cases of blepharitis are not rare as was shown by the Piedmont 
commission. Often also diplopia, photophobia, and synchysis are 
found. Many pellagrins remain for years with their eyes closed for 
fear of the light. Early cataracts are found among the pellagrous ; 
and pterygium is not infrequent. Doctor Ottolenghi, with Pro- 
fessor Manfredi and Doctor Flarer have made ophthalmic studies 
on pellagrins. Their results are given in the following table : 

Number examined 36 

Depth of eye normal 12 

Changes in the retina 15 

Atrophy of arteries 12 

Anomalies in fundus of left eye 1 

Anomalies in fundus of right eye- 6 

Atrophy of optic nerve 3 

Increase of pigment 3 

Dilatation of the veins 1 



GENERAL CHARACTERISTICS OF THE DISEASE 159 

" Fifteen of these cases showed retinal changes by a yellow or 
gray reflex in one or both eyes — a sign of precocious senility ; it 
is of interest to note that there were three cases of white atrophy 
of the papilla?, among which was one case of retino-choroiditis in 
an advanced stage. Ottolenghi found also in three pellagrins one 
light case of papillitis, more pronounced in the left eye ; in the 
second case pronounced gray atrophy and diffuse retino-choroiditis 
of the two sides; the third was normal. It is of interest to note 
the observation that in several individuals the ocular fundus dif- 
fered on the two sides. This, however, cannot be given as a reason 
for the numerous pupillary inequalities since these are noted in 
individuals who show a normal fundus. However, the unilateral 
anomalies of the fundus as well as those of the pupils predominate 
in the right eye and consist in lesions of the arterial vessels with 
papillary and retinal changes. Rampoldi observed pellagrous 
ocular troubles principally in the autumn or the spring, and found 
that they consisted of organic lesions rather than functional dis- 
orders. The retina and optic nerve shew more than any other part 
of the eye the pellagrous cachexia ; next come the cornea and lens ; 
finally, the choroid and vitreous body. Hemeralopia and pigmen- 
tary retinitis are not rare. Torpid ulcers of the cornea are found 
with essential hypertonus of the bulb and scintillating synchysis of 
the vitreous." 

Whaley found shallow anterior chambers in 33 out of 35 cases 
examined ; there was some dilatation of the pupil, but it was not so 
prominent a symptom as noted by the Italian writers ; in 6 cases 
was seen photophobia ; dilatation of the retinal veins and a yellow- 
ish reflex from the retina was noted and the observer had never seen 
the same condition in any other class of cases. Arterio-sclerotic 
changes also occurred in all degrees affecting the young as well as 
the old. Partial vertical homonymous hemiopsia has been recorded. 

The senses of taste and smell have been found normal in all 
cases in which the patient was mentally competent to give intelli- 
gent replies. 

It has been noted that salivation is a frequent accompaniment 



160 



A TREATISE ON PELLAGRA 



of the stomatitis of pellagra. The salivary glands are usually very 
active and the saliva is found to be acid. 

The study of feces in pellagra by the Illinois State Board of 
Health showed protozoal infection in S4.8 per cent of the cases 
examined. This consisted of amebse and flagellate and encysted 
forms. It was thought that these protozoal infections account for 
a large portion of the intestinal symptoms. In another place the 
work of Allen has been referred to at some length. There seems 
to be growing up in the South a tendency to attach more than pass- 
ing attention to the frequency of amebiasis in pellagra and the 
subject deserves more attention. It becomes a question whether or 
not amebse occur in health in the sections where pellagra is occur- 
ring and what part they play in a pathologic process after the in- 
testinal lesions of pellagra appear. It would seem that this high 
percentage of occurrence is more than accidental. 



CHAPTEK IV 

SKIN MANIFESTATIONS 

The most important symptom of pellagra is the skin mani- 
festations. Without this symptom, under ordinary conditions, 
the diagnosis should never be made. This rule should, at 
least, apply to this country, where the disease is still so 
little recognized, until a better knowledge is acquired. As a 
rule, pellagra appears in rural localities where skin diseases are 
comparatively unusual and the country physician consequently 
has a more limited acquaintance with such conditions. With this 
fact in mind it will be attempted in this chapter to consider this 
group of symptoms more from the standpoint of the general prac- 
titioner for whom this work is especially intended. The derma- 
tologist will find it very elementary and from his standpoint open 
to many serious objections. As a rule pellagra seldom reaches 
the dermatologist and, further, it should not be considered a skin 
disease. As far back as the time of Strombio, the elder, the fact 
was recognized that the skin features were merely the symptoms 
of a general condition, just as the eruption in syphilis is merely 
a symptom to be known and recognized by all divisions of the 
profession regardless of his specialty. The eruption in pellagra 
is more important even than the eruption in syphilis, because in 
the latter disease when there is a doubt about the diagnosis, the 
Wasserman reaction may be resorted to and the result be abso- 
lutely relied on. In pellagra there is no serum test. 

It is well at this place to consider the question of pellagra 
without skin manifestations, or the so-called " pellagra-sine- 
pellagra." This question has occupied my attention for a long 
time, and I have finally concluded that such an occurrence is 
highly improbable and that the explanation of such a description 



162 A TREATISE ON PELLAGRA 

in the literature was to be found in the fact that at times the 
eruption in pellagra is so insignificant as not to attract attention, 
even from the patient. It is no unusual thing in securing a his- 
tory in such cases where there is reason to suspect pellagra that 
on cross-questioning one will learn that during the past summer 
the patient did have a rather severe sun-burn which was not of 
sufficient consequence to be mentioned. If is well recognized that 
the eruption in scarlet fever may at times be so insignificant as 
not to be detected until the appearance of an acute nephritis or less 
frequently until the discovery of a desquamation, rnfortunately. 
in pellagra the insignificance of the skin lesion in no way indi- 
cates a mild attack. Many of the most severe and even fatal cases 
have the most insignificant skin symptoms, while on the other 
hand " pellagra universalis," <>r pellagra with a genera] distri- 
bution of the skin lesion over all or a large portion of the skin 
surface, may occur in the very mildest cases. In Xorth Carolina 
there have been more recoveries in cases of pellagra universalis 
than in any other class of cases. The converse is not necessarily 
true. We have been told that in the London School of Tropical 
Medicine the students are taught to diagnose pellagra without the 
presence of the skin manifestations. Certainly such teaching 
would be unwise in the southern states, if for no other reason than 
because of the fact that in this region there also occur sprue. 
Cochin-China diarrhea, and amebic dysentery. Sprue, especially, 
complicates the question, for the reason that its symptoms, except 
for the absence of skin manifestations, are almost identical with 
pellagra. After a careful study of the two diseases one is unable 
to distinguish so-called " pellagra-sine-pellagra " from sprue. It 
is highly probable that cases have been called sprue when they 
were really pellagra with inconspicuous skin lesions. For the 
sake of conservatism it is wisest to count the skin manifestations 
of pellagra as the pathognomonic symptom. It may be that in so 
doing some cases of pellagra will go undiagnosed, but this num- 
ber will be gradually reduced as the physician becomes more and 
more familiar with the disease and the possibility of its occur- 
rence. It will soon be the rule to have this possibility in mind 



SKIN MANIFESTATIONS 163 

when examining patients with obscure functional nervous disturb- 
ances or depressive mental states, especially when there is added 
digestive disturbances. In such cases a careful inquiry will often 
be repaid by the discovery that there was an erythema some 
months previous, or else there may be found definite traces of 
an old symmetrical exfoliation. This latter may only manifest 
itself by the presence of a faint line, which will later be referred 
to as a sign of the greatest diagnostic value. It should never be 
overlooked that the skin manifestations of pellagra only occur 
during a very short period and that the remaining symptoms of 
both nervous and gastrointestinal type will persist and often 
call for the greatest care on the part of the physician in making 
a correct diagnosis. These are really cases of " pellagra-sine- 
pellagra," which goes to show that this term is oftentimes a mis- 
nomer. I have in mind a very typical case of pellagra which 
I saw through the courtesy of Doctor Bigger of Rock Hill, South 
Carolina. Some time after our consultation it became necessary 
to remove the patient to an institution in the North, and I was 
called on by my colleague to bear him out in his diagnosis, as 
the authorities of the institution were unwilling to accept the 
diagnosis without the presence of the skin manifestations. There- 
fore, it will be readily appreciated that in no other condition is 
a careful history of so great importance. 

The time of the appearance of the skin manifestations in the 
course of the development of pellagra is subject to many variations. 
In typical cases the ordinary sequence is for the skin lesions to 
follow the onset of the stomatitis and diarrhea, though either of 
these latter symptoms may be wanting. There are many instances 
where the diarrhea and cachexia as well as gastric disturbances 
have existed for several years before the appearance of sufficient 
skin indications to settle the diagnosis. In other cases the ery- 
thema may appear for the first time after the commitment of the 
patient to an institution for the insane. I have under my care a 
woman who claims to have had diarrhea all her life. She is fifty 
years old. Certainly for the past five years the mouth and in- 
testinal symptoms have strongly suggested pellagra, but it has 



164 A TREATISE ON PELLAGRA 

been possible to confirm this suspicion only within the past few 
months by the tardy appearance of a slight symmetrical erythema 
of the backs of the hands. One of my first cases was a man who 
had been demented and committed to an institution for many 
months before the erythema appeared. His first symptom was 
mental apathy and confusion. This was followed by diarrhea. 
The erythema was the last symptom. Another patient had been 
in an insane institution for several years when she was given 
a furlough to go home. It was on this visit that pellagra was 
discovered. Her brother died after having been bedridden many 
months with dementia, diarrhea alternating with constipation, 
stomatitis, and emaciation. In this case no erythema was de- 
tected, though looked for daily over a period of more than a year. 
If ever the diagnosis " pellagra-sine-pellagra " was justified, this 
was the time. 

Four years ago a man, aged fifty-six, consulted me on account 
of an indefinite gastric neurosis. . He was frightened away by the 
mention of the stomach tube for the removal of a test meal and 
was lost sight of until last June, when he returned. At this time 
he had the first definite pellagrous erythema of the backs of his 
hands, accompanied by diarrhea and stomatitis. There can be 
no doubt that his past vague symptoms were those of an atypical 
pellagra. In such a case the diagnosis could not have been made 
until the appearance of the skin symptoms, which were absent 
until the case had become almost hopeless. 

The only feature of the skin manifestations of pellagra that is 
really distinctive is the symmetry. The character of the skin 
condition itself may suffer many variations, but symmetry uever 
fails. Without it the diagnosis should never be made. Any 
asymmetrical skin lesion should be classified differently, for it 
is not pellagra. Before the consideration of any other feature 
a pellagrologer examines the two symmetrical parts, it matters 
not where the skin lesion may be located. An erythema of one 
hand or one foot is never pellagrous. This symmetry is not re- 
stricted to the location of the patch of erythema ; it also includes 
symmetry of size and shape. If a pattern of the skin lesion were 



SKIN MANIFESTATIONS 165 

made of one side it would be found to conform exactly, in most 
instances, to the lesion of the other side. In no other disease does 
such symmetry occur, and in itself it is almost pathognomonic of 
the type of skin lesion. It will be found that the lines of de- 
marcation between normal and diseased skin are symmetrical in 
position and direction. Whatever angle is assumed by this line 
on the right forearm will be reproduced on the left. If there is 
a patch of erythema on the right elbow no larger than a split pea 
it will be reproduced on the left elbow in the corresponding spot 
and be of the same size and shape. If an exact measurement of 
the limits of the erythema is made of one side it will be found 
not to vary by a quarter of an inch on the other side. This is 
illustrated by measuring from the tip of the styloid process to the 
upper limit of the lesion and comparing it with the same measure- 
ment of the other side. Casal observed this feature, and the 
copper plate, Fig. 1, in the first chapter, quaintly demonstrates 
it. Since his time all observers have acknowledged the impor- 
tance of this feature of the disease and none have ever questioned 
it. In spite of this fact it is notable that too little importance is 
attached to it. When the scourge appeared in such serious form 
in the southern states in 1905, long before it was identified as 
pellagra, this one symptom was universally noted and suggested 
to many a nervous origin. Fig. 22 depicts a foot of a man 
who died of pellagra. There is nothing distinctive of the disease 
in this picture, and certainly a diagnosis of pellagra would not 
have been made had this been the only skin manifestation, but 
there was also a symmetrical erythema of the hands (Fig. 23). 
There was for a long time a doubt in my mind if this really was 
a pellagrous manifestation, but observation and the teaching of 
Merk lead me to accept it, having in mind that the symmetry 
of the lower extremities is not so marked as in the upper, and 
also that the other limb showed a much slighter lesion in the 
corresponding part. It seems that to complete this picture of 
perfect symmetry the action of sunlight must be added. In the 
lower extremities the sun seldom having any direct action, the 
erythema is not so well defined, either as to symmetry or to 



166 A TREATISE ON PELLAGRA 

the sharpness of the line of demarcation between normal and 
diseased skin. The attention of the reader is directed to the 
accompanying diagrammatic sketches showing the areas of skin 
involvement. It will be noted that this symmetry is strictly ad- 
hered to in every instance. These are not selected cases, but are 
true representations of the conditions as they exist. When in doubt 
of a diagnosis the chances of error will be greatly lessened if this 
symptom is held clearly in mind, for such symmetry has never 
been imitated in medicine. One of my patients had a patch 
of erythema no larger than the cross section of a lead pencil 
at the outer canthus of the right eye. The case was watched with 
unusual interest to see if the symmetry would be carried out. 
In a few days there appeared at the corresponding position of 
the other side an area of the same size and shape. It will be 
noted that the pectoral extension of the Casal collar is placed 
exactly symmetrically and its tip is exactly in the mid line of 
the body. 

Our knowledge of the location of the pellagrous erythema had 
its origin chiefly in the writings of the Lombardian and Venetian 
physicians, and even to-day their view is largely adhered to in 
many details, though they did not seem to appreciate the impor- 
tance of the erythema in its unusual positions. Frapolli in 1771 
gave a very concise account of the ordinary type of the skin 
lesions. He described it thus :".... manus denique, pedes, 
pectus, raro etiam facies, ea?tera?que Corporis Soli, exposita? 
partes turpiter foedantur." * 

Odoardi, who confused the disease with scorbutus because of the 
affection of the mucous membrane of the tongue and mouth, ac- 
cepted the account of the Casal collar from a French translation 
of Sauvage's " Nosology," without tracing it back to its real 
author. He did, however, begin a more accurate manner of de- 
scribing the locations of the skin lesions. For example, in place 
of saying that the lesion was of the hands, he added the more 

1 " Physici Francisci Frapolli Mediolanensis Nosocomii majoris mediei ani- 
madversiones in Morbum, vulga Pellagra." Mediolani, 1771. See also Merk's 
" Hauterscheinungen der Pellagra." 



SKIN MANIFESTATIONS 167 

exact backs of the hands. We are indebted to him also for first 
mentioning the feet as a situation for the lesion. His statement 
that the erythema did not appear in this situation until the disease 
had existed for three or four years has not been borne out in my 
experience, for I have seen the feet and legs of children affected 
with the first outbreak. 

Raymond later wrote a more exact description of the skin mani- 
festations in which he described the areas affected and the lines 
of demarcation between normal and diseased skin. But it was 
not until some years later that it was recognized that the erythema 
might appear on the covered portion of the body as perianal and 
perigenital regions. Merk, to whom we are indebted for the 
most complete and accurate account of the skin manifestations of 
pellagra and to whom I am largely indebted for much of the 
information in this chapter, divides the skin lesions into the 
usual locations and the unusual locations. This will be adhered 
to in this chapter for the sake of simplicity. 

Next in importance after symmetry is the distribution of the 
skin lesions. The relative frequency of the various situations 
is shown in the following table of Merk's : 

1679 cases/ or 77 per cent, with erythema of the backs of the 

hands alone. 
282 cases, or 13 per cent, with erythema of the backs of the 

hands and the neck. 
164 cases, or 7.5 per cent, with erythema of the neck. 
53 cases, or 2.4 per cent, with erythema of other parts of the 

body. 

In a series of my own the following was noted. The number of 

cases was 189. 

182 cases, or 95.3 per cent, with erythema of the backs of the 

hands. 
36 cases, or 19 per cent, with erythema of the neck. 
4 cases (all children), or 2.11 per cent, with erythema of the 

feet only. 



168 A TREATISE ON PELLAGRA 

It will be seen that the hands are more commonly affected than 
any other part. In pellagrous countries the physicians, as a rule, 
are content to base their opinions on the appearance of this part 
alone. This is well illustrated in the museum specimens of pella- 
gra, which only include the diseased hands and forearms. In 
1881 Hardy and Marchand described five cases : four showed the 
hands alone affected and the fifth showed the tongue. In only 
5 per cent of my own cases was the lesion of the backs of the 
hands lacking, and most of these patients were children, who were 
accustomed to going without any covering to their feet and legs, 
thereby exposing these parts to the sun equally as much as the 
hands. It is safe to say that in this country, at least, not more 
than 1 per cent of the adult cases fail to have the lesions of the 
hands. 

The erythema of the backs of the hands may occur as round 
spots about the size of a half dollar, which are separated by areas 
of normal skin. These areas of diseased skin may become con- 
fluent. In other cases the area of skin affected is more spread out, 
covering the entire back of the hand. Laterally and medially the 
erythema stops sharply on the line where the sweat glands begin, 
and does not, except very rarely, involve the palms. This ery- 
thema extends up the forearm and ends with a sharp line of 
demarcation on the extensor surface. Sometimes the erythema 
extends the whole length of the forearm, while again it may ex- 
tend only two or three inches above the wrist. In some eases the 
skin involvement is limited to a chaffing of the knuckles and is 
often so slight as to attract no attention. In some cases the upper 
limit of the erythema is situated between the wrist and the carpo- 
phalangeal articulations, as is seen in Fig. 10. It is not unusual 
to see an anterior extension just above the wrist occupying the 
position of the pronator quadratus muscle. The involvement of 
the upper portion of the forearm and the arm may occur. It is 
a generally recognized fact that in women the extent of the skin 
involvement is greater than in men, and is no index to the gravity 
of the case, as has been mentioned. The involvement of the fore- 
arm is frequently in the shape of a triangle, with the base at the 




169 



170 



A TREATISE ON PELLAGRA 



wrist and the apex at a varying point on the external surface of 
the forearm. Occasionally the lesion extends around the forearm 
to the anterior surface, being continuous throughout and thereby 
forming a much larger triangle, which is wrapped around the 
part. 




Fig. 10. — Case of Dr. C. H. Lavinder in the U. S. Marine Hospital at Staple- 
ton, N. Y. Note limited area of erythema. 



Raymond was the first to call attention to the fact that there 
is a tendency for the last two phalanges of the fingers to be spared 
by the erythematous process. This observation was not confirmed 
by the South Carolina observers (Lavinder and Babcock). In 
North Carolina we have seen many illustrations of this absence 
of the lesions on the ends of the finders, but, on the other hand, 



SKIN MANIFESTATIONS 171 

we have also seen many cases with the lesions extending to the 
edge of the nails, resulting, in some cases, in an atrophic condition 
of the ends of the fingers, which suggests the appearance of the 
fingers of a cadaver which has lain on the dissecting table for some 
time. The nails are never damaged by the pellagrous lesions. 
As a rule the palms of the hands are spared, but even to this rule 
there are exceptions, some of which I have seen. However, pella- 
gra cannot be said to affect this part but very exceptionally, prob- 
ably not more than in one-half of one per cent of the cases. In 
the United States many writers have emphasized the points of 
the elbows as a frequent location of the erythema. Such has 
been my experience, but it is important not to confuse it with 
a simple irritation and roughness of the skin produced by the 
contact with such an object as a table or arm of a chair. Such 
mechanical irritation in an emaciated patient especially could 
be easily confused with pellagrous erythema. The normal skin 
is often even covered by a callous produced by this means. The 
" pellagra gauntlet " is often described, but is not as common a 
finding as one would suppose from the frequency of this reference. 
In this gauntlet the upper border is at right angles with the arm, 
passing across the forearm at a point about midway between the 
wrist and elbow. This is well illustrated in Fig. 6, which shows 
the lesion on the posterior surface of the forearm. To form this 
gauntlet the anterior surface must also be involved. 

The arm, while not usually affected, does not always escape. 
When it does become involved the most frequent seat of the lesion 
is the outer aspect near the shoulder. In one of my cases such 
a lesion occurred. In this case the erythematous process extended 
over the whole of the posterior surface of the hands, forearms, 
and arms, and nearly all the anterior surfaces of the arms except 
a small area at the elbow. The lesion was of the dry exfoliative 
type, with the characteristic brown pigmentation. In addition 
to these areas the process began over the upper portion of the 
sternum and extended upward and outward, encircling the an- 
terior aspect of the neck. Posteriorly the back was covered by 
the same lesion from the hair margin to below the angles of the 



172 A TREATISE ON PELLAGRA 

scapulae, leaving a central strip of normal skin and also two 
areas over the shoulders corresponding to those portions covered 
by the shoulder straps of the chemise. This case was of great 
interest, for it so well illustrated the part played by solar influence 
in the production of the erythema. It recalls the experiments in 
which the observer produced spots of erythema of whatever size 
and shape he pleased by cutting out such patterns from the gar- 
ment worn by the patient and exposing the bare skin to the action 
of sunlight. 

More frequently than observed by Merk does the erythema 
involve the neck in the cases seen in this country. In 19 per <•< nt 
of my cases the neck was at least one of the locations of the ery- 
thema. The lesion here varies greatly. In some cases there are 
two symmetrical areas on the back of the neck equidistant from 
the mid line. In other cases the outline of the lesion corresponds 
to the outline of the exposed portion of the skin, as in cases where 
a low-cut neck or V-neck is worn. This involvement is not always 
confined to that portion entirely bare, but may also include a 
portion which is covered by only some thin form of clothing. 
In other cases the lesion is limited above by the hair line and 
below by the vertebra prominens and passes around the neck, meet- 
ing in front either as a broad band or else as a gradually nar- 
rowing strip. This broad band anteriorly often has extending 
downward from it over the manubrium a process which was de- 
scribed by Casal. Merk describes the Casal collar as beginning 
at the nape of the neck a little below the hair margin and passing 
diagonally around the neck parallel with the lower jaw and several 
finger breadths from it. On a level with the larynx the two sym- 
metrical processes meet in the mid line anteriorly. The lower 
border may begin somewhat below the vertebra prominens and 
keep close to the root of the neck, uniting with the corresponding- 
portion over the upper part of the manubrium. This produces 
quite a wide collar, which is often characterized by an irregular 
upper border. Fig. 7 depicts the collar in a negro girl of eleven 
years. This collar is much more frequently found in women and 
children than in men. In the latter it is quite unusual. One 



SKIN MANIFESTATIONS 173 

of Merk's cuts shows the last remnant of a Casal collar in a 
man. I have never seen the Casal collar in a man. Merk says 
that the entire collar may be merely a line hardly a finger breadth 
in width or it may be incomplete. Sometimes this incompleteness 
may be combined with imperfect development. The collar may 
be deficient either anteriorly over the larynx or posteriorly. What- 
ever portion of the collar is present is distinguished for its abso- 
lute symmetry. The process extending downward from the Casal 
collar over the manubrium is known as Casal's appendix fasciola. 
Above at its origin it is broad, covering the sterno-clavicular 
region and gradually tapers downward, ending in more or less of 
a point. It sometimes reaches as low down as the level of the 
nipple. Merk only observed this appendix of Casal in men, and 
states that he does not know of its occurrence in women and chil- 
dren. He further states that this collar is never observed alone 
without a like lesion of some other portion of the skin surface. 
Five years ago, in my experience, it was an every-day occurrence 
to find cases with the erythema of the neck, but as time went on 
the number of such cases became greatly lessened, until now when 
such a case is a rarity, though the number of diagnoses of pellagra 
is by no means decreasing. 

In one of Zeller's cases reproduced by Hyde there is shown an 
extension downward from the posterior aspect of the Casal collar. 
This same peculiarity was seen in one of my female patients, 
which is represented diagrammatically in Fig. 12. In this 
case the process was from more than a Casal collar, as the 
erythema extended over a large part of the back as well as an- 
teriorly over the whole chest wall as low as the mammary region. 

The lower extremities are rather infrequently the seats of 
pellagrous erythema. The cases reported are chiefly from the 
southern states. In. European literature little attention is paid 
to this location. It has been stated by Merk that the erythema 
never appears on the feet or legs without an appearance on other 
portions of the body. I have seen exceptions to this rule in 
children, and have in mind, especially, the case of a child twenty- 
two months old with a typical symmetrical pellagrous erythema 



174 A TREATISE ON PELLAGRA 

of the feet and lower legs, forming the so-called " pellagrous 
boot." The lesion was absent from all other portions of the body 
at that time and never appeared later. Usually the line of de- 
marcation proximally of the erythema of the feet passes across 
the tops of the feet in the malleolar region separating the anterior 
portion which is affected from the posterior portion which is 
usually not involved in the process. The heel is never the seat 
of any form of pellagrous affection. Sometimes the erythema 
ends itself without involving the toes. In other cases it passes 
on, including the toes as it included the fingers. Merk noted 
that the toes were not equally involved. The great toe, according 
to him, is affected up to the very nail ; the second toe only to the 
first interphalangeal joint ; in the third and fourth the uninvolved 
end is relatively greater; finally the fifth toe remains uninvolved. 
There are exceptions to this rule, but it may be expected that 
the great toe will be more involved than any other. Fig. 11 
shows the feet of a negro, and here all toes are affected. In 
patients in bed suffering with erythema in other parts of the 
body I hare watched from day to day with great interest the 
gradual development of the lesion on the toes. In such cases 
the great toe does not suffer so much as in the experience of Merk, 
but relatively I have noted that the fifth toe was more completely 
covered by the erythema. In the light of Merk's greater ex- 
perience I would have to regard this condition noted by me as 
rather exceptional. It is no unusual thing to find the skin of the 
tops of the feet affected in adult pellagrins who are bedridden 
and whose feet and legs cannot be exposed to the sun. But in 
such cases there is a departure from the usual character of the 
skin affection. This is chiefly seen in the line of demarcation of 
normal from diseased skin which is not so well defined. The 
appearance is often that of an inflammatory condition of the 
lymphatic vessels, with the accompanying streaks extending up 
the legs. There is nothing distinctive of pellagra in the lesions 
of this locality, so that in the absence of the lesion elsewhere the 
diagnosis of pellagra could not be made. As before stated in chil- 
dren who do not wear shoes and stockings, the nature of the 



SKIN MANIFESTATIONS 



175 



erythema of the feet and legs is the same essentially as in the 
erythema of the other parts, but especially the hands. The line 
of demarcation between the normal skin above and the diseased 
below in such cases is just as sharply defined as in the hand and 




Fig. 11. 



Skin Lesion of the Feet. The Lesion Extends to the Nails. 
tesy of Dr. J. W. Babcock, Columbia, S. C.) 



(Cour- 



forearm lesions. In my experience in such cases the symmetry 
is as marked as in any other part, but Merk found that this was 
not so well carried out in his cases. He says that the proximal 
border has various manifestations. In one man he found the 
lesion winding around the lower leg, as was described as occurring 



176 



A TREATISE ON PELLAGRA 



in the upper extremity. Usually the involvement includes only 
the foot, less frequently the foot and lower third of the lower 
leg, and sometimes in children reaches higher towards the knee. 
A symmetrical patch of erythema above the patella or below it or 
in both positions frequently occurs. This is illustrated in Fig. 12. 




Fig. 12. — Areas of Distribution. 

I have known the erythema to occur on the outer aspect of the 
thigh about the middle and to be as large as two palms. This 
is very exceptional and deserves no mention among the usual 
locations. 

The lesions of the face are of two kinds. In one, the so-called 
pellagrous mask, the skin is diffusely affected. In the other the 
lesion occurs in isolated patches separated by normal skin. The 



SKIN MANIFESTATIONS 177 

pellagrous mask may be of mild degree with little deformity, but 
again it may be of the moist variety with considerable exudation, 
and then there results more or less contraction of the skin resem- 
bling the condition produced by burns. This is well illustrated in 
Fig. 6. In this case the contraction of the skin was so great 
that the child had not been able to close her eyes or her mouth 
completely for weeks. The diffuse type limits itself to the por- 
tions uncovered by hair and between the hair margin, and the 
border of the erythema is a narrow strip of unaffected skin. In 
the case shown in Fig. 6 the lesion involved the ears and all 
other portions of the head except the scalp. The extent of the 
skin involvement differs in different cases. In all cases in this 
locality the symmetry is especially well marked and there are 
no exceptions. The most usual location is the ala of the nose, 
after this the other portions of the nose, then the forehead, cheeks, 
and chin. Occasionally the lips and more rarely the eyelids and 
ears are affected, according to Merk. The erythema often has a 
serpiginous, wavy border, which is well illustrated in some of 
Merk's cuts. My own cases have more commonly shown a ten- 
dency for the formation of spots of erythema. One of the favorite 
locations for these spots is the outer canthus of the eye. Some- 
times there are two symmetrical areas on the forehead of varying 
size placed equidistant from the mid line of the body. Merk says 
that the degree of erythematous redness of the face is not often 
extreme and may be easily overlooked even when sought for. 
The attention is usually not directed to it until after defervescence, 
when the brownish pigmentation marks the location and extent 
of the previous erythema. But even these secondary changes may 
be so inconspicuous as to be overlooked. This is said to explain 
the absence of any mention of it in the writing of Casal. Frapolli 
merely mentions the fact in these words: "'.... pectus, raro 
etiam fades, .... turpiter foedantur." Raymond's descrip- 
tion was much more accurate, but even he failed to give 
the location proper consideration. He said : " In children 
it shows itself on the forehead, the cheeks, the nose. This 
feature is shown chiefly in women and rarely in men." This 



178 • A TREATISE ON PELLAGRA 

latter observer noted the condition in a Hungarian soldier. 
In Mexico, Camara Vales noted the fact that the face- of men 
were more liable to this affection than the faces of women. The 
pellagrous mask is said never to have occurred independently, but 
is always found in cases where the erythema exists in some other 
location. I know of no exceptions to this rule. 

According to the authority of Merk the knowledge of atypical 
localization of the pellagrous skin lesions is of a very recent date. 
This is accounted for by the belief of the older observers that 
the action of the sun's rays was essential in the production of the 
condition. Deiaco was the first to describe the occurrence of the 
erythematous process on the external genitalia of pellagrous 
women. Before this, however, pellagrous inflammation of the 
vulva and vagina was known (Merk). A few years after this 
publication of Deiaco's he described more unusual localizations, 
mentioning the fact that Stefanowicz claimed priority in this 
connection. Merk considers the division into usual and ex- 
traordinary to be purely arbitrary, varying with each observer. 
For example, he says that Raymond would consider the involve- 
ment of the skin over the last phalanx of the finger as atypical, 
while he would consider it usual. Atypical localizations may 
occur in cases with other typical localizations, thereby rendering 
the diagnosis much less difficult. Merk includes with unusual 
localizations a pellagrous mask with a well-defined Casal collar 
in a man. Certainly this is rightly classified, for it is not 
possible in such a subject to find a more unusual condition. 
It has never occurred in my experience. He also describes a peri- 
anal lesion which extends from one cheek of the buttocks to the 
other and from the sacrum to the perineal region. Such a 
location is not so unusual in the American cases. I have seen 
erythema in elderly people occupying this exact location which 
was not pellagrous or even suggestive of it. Hence it is im- 
portant to apply the rule never to diagnose pellagra by any 
but a typical skin lesion. Merk also counted as atypical the 
incomplete Casal collars. Many such cases have occurred in 
my experience, but their symmetry made the diagnosis simple 




Fig. 13. — Dr. Zeller's Case, Showing Remarkable Distribution and the 
Lamellated Appearance. (Reproduced through the courtesy of the Illinois 
State Board of Health, Dr. J. A. Egan, Secretary.) 

179 



180 



A TREATISE ON PELLAGRA 



enough. Often the only portion of this collar present consists 
in two symmetrical areas equidistant from the mid line on the 
back of the neck. Deiaco 1 described a case in which a strip of 
erythema appeared over the acromium and covered the lateral 
half of the entire arm with the flexor and extensor surfaces re- 
maining free. More remarkable than this is a case reported in 
the Monthly Bulletin of the Illinois State Board of Health (see 
Fig. 13). As will be scon, the lesion extends from the point 
of the shoulder on the antero-external surface of the arm down- 




Fig. 14. — Atypical Localization on Knees. (After Deiaco from Merk.) 



ward to the point of juncture of the middle and lower thirds of 
the arm. The symmetry of this case as well as Deiaco's is very 
striking. Deiaco described another case with the involvement 
on the shoulders entitling it to the term epaulet. Merk gives 
a diagram (Fig. 1-1), representing the lesion corresponding to 
the patella in shape and size with a wavy outline. Sometimes 
the lesion of the anterior surface of the knee is prolonged down- 



ward over the tibia in a sort of tongue reaching to the middle 
of the lower leg. Again, as seen on one of Merk's beautiful 
colored plates, the lesion may occupy the posterior surface of 



1 Deiaco, Pius, " Beitrag zur Symptomatologie der Pellagra," Wiener klin. 
Wochr., 1905, and " Ueber Lokalisation u. Natur der pellagroesen Hautsymp- 
tome," 1907. 



SKIN MANIFESTATIONS 



181 



the knee in the bend thereof. There may be a lesion over the 
elbow with a tongue extending downward some distance over 
the ulnar (see Fig. 15). 

Fig. 16 shows another of the interesting cases of Merk's in 
which the scrotum is affected. It is noticeable that on both 
sides of the raphe the erythema extends outward in perfect 
symmetry. 





Fig. 15. — Atypical Localization on Elbows. (After Deiaco from Merk.) 



Fig. 17 shows diagrammatically a case of my own in a 
young woman who was not seriously affected and who afterwards 
made a complete recovery. The skin lesion covered the whole 
of her back from the lower border of the scapula up to the very 
hair border of the neck and anteriorly from the upper portion 
of the breast to the chin. The remarkable feature of this case 
is that where the chemise shoulder straps crossed the shoulders 
there was no skin involvement at all. Fig. 12 shows another 
extensive involvement of the skin of the neck and pectoral region 
anteriorly and posteriorly, with a tongue extending downward 
from the posteria area exactly in the mid line. Fig. 18 shows 
the areas of involvement in a boy of fifteen years. There was 



182 



A TREATISE ON PELLAGRA 



beneath each scapula a sharply defined, somewhat triangular area 
of erythema distinctly symmetrical. There seems to be no limit 
to the number and variety of these atypical localizations and a 
further account of them would be superfluous. Suffice it to say 
that the lesson drawn from the occurrence of such conditions is 




Fig. 16. — Atypical and Very In- Fig. 17. — Extensive Skin Involvement, 
frequent Localizatiox on the Author's Case. Note areas of uninvolved 
Scrotum. (After Deiaeo from Merk.) skin. 

that the whole skin surface should be examined in every case of 
pellagra — not so much for diagnostic purposes, for, as a rule, 
they are not depended on for such a purpose, but merely from 
a dermatological standpoint in order that these peculiarly placed 
erythemata may be classified where they belong. As mentioned 
on a previous page and depicted in Fig. 22. I have seen such 
lesions where the only means of identifying them as pellagra 



SKIN MANIFESTATIONS 



183 



would be that there existed coincidentally other erythematous 
areas which were typical in their general character and localization. 
The character of the skin lesion per se is the least important 
feature, and cannot be depended on in arriving at a diagnosis. 
It is subject to a multitude of variations of an indefinite character, 





Fig. 18. — Author's Case. Note 
areas below scapulae. 



Fig. 19. — Areas of Distribution. 
(From Merk after Deiaco.) 



lacking that exactness seen in syphilis, though this disease, too, 
is subject to many variations in form. These forms, however, 
follow a definite rule and in themselves furnish valuable aid in 
the diagnosis. 

The lesion of pellagra is usually referred to as an erythema, 
but this term must of necessity be used in a very broad sense 



184 A TREATISE ON PELLAGRA 

to include all classes of cases. There are probably just as many 
cases which should rightfully be classified under the term derma- 
titis. Dyer has pointed out that in a number of cases under his 
observation the skin changes without regard to localization could 
be typical of blastomycosis, of the erythema multiforme group, 
and of a number of other conditions. He distinguished it from 
vesicular eczema by the appearance and persistence of vesicles 
in the latter as well as by the development of papillary areas and 
the marginato, erythematous, elevated, and infiltrated border, all 
of which point to a deep-seated affection which begins deep and 
is not merely a catarrhal process started in the mucous layer. 

The first change noted is often distinguished with great diffi- 
culty from simnle erythema of sunburn. Hyde has pointed out 
that the pellagrous erythema is more reddish than pinkish and that 
it is rare for this identical shade of color to be reproduced in a 
blonde by the action of the sun. lie also stated that discreet 
macules often occur which speedily fuse and produce a uniformly 
smooth, reddened, and distinctly outlined surface suggesting the 
appearance of a glove when the hand is the portion affected. In 
a large experience I have never developed such skill that I could 
differentiate a recent sunburn from a recent attack of pellagrous 
erythema. Such a distinction requires a keener appreciation of 
color differences than is possessed by the ordinary general prac- 
titioner and must be 'left to the experienced dermatologist. Not 
a few cases of solar erythema have been regarded suspiciously by 
me and my colleagues. I well remember a case of Bellamy's in 
which he was undecided between the two possibilities for several 
days, though the child was well nourished and a member of a 
family living in the very best conditions. Certainly there could 
not be found a better simile than to compare pellagrous erythema 
with sunburn, and to one who has never seen the former disease 
no clearer conception could be had than to fix the mind's eye 
on the latter condition. 

Merk in his work above alluded to says that in the beginning 
of the skin manifestations there is a preliminary rash of dis- 
creet macules, which persists from a few days to several weeks. 



SKIN MANIFESTATIONS 



185 



Some writers say that after a few days the skin becomes covered 
with scales and exfoliating epithelium. Such is not my experi- 
ence. As before stated, I have watched the appearance of the 
erythema from the very beginning in a study of the symmetry 
of the condition. In this watching for the very first signs of 
the erythema in the expected locality to conform to the rule of 
symmetry, the erythema could be minutely studied. There are 





Fig. 20. — Areas of 
Distribution. (From 
Merk.) 



Fig. 21. — Areas of Distribution. (From 
Merk's "Die Hauterscheinungen der Pel- 
lagra," after Deiaco.) 



some cases, doubtless, which follow this rule of Merk's, but there 
are others which begin as a mere blush without even as much 
of the macular features seen in the ordinary scarlatina and, in 
fact, I was unable to detect any macular indications of any 
kind. Regarding the exfoliation it is certainly not the rule in 
this country for it to follow so closely on the wake of the ery- 
thema. Usually the exfoliation does not supervene until after 
there is a very definite pigmentation of the skin. Even Strombio 
stated that after a few days all skin manifestations disappear. 



186 A TREATISE ON PELLAGRA 

It is apparent that there are cases in which the term erythema 
truly describes the skin lesion, while there are other cases which 
even from the beginning cannot be accurately classified under this 
head. In this connection Howard Fox 1 says : 

" The name erythema, by which the eruption of pellagra is gen- 
erally denoted, does not appear to me to be entirely appropriate. 
It would seem quite proper to use the term erythema for the 
first stage of the disease, which resembles ;m ordinary sunburn, 
and which lasts only a few days. But it seems somewhat anoma- 
lous to speak of the entire eruption as an erythema when the 
erythematous stage is so comparatively insignificant, while the 
stage of desquamation is so characteristic and of such long dura- 
tion. An eruption which is called an erythema conveys the idea of 
affections such as erythema multiforme or the so-called toxic 
erythemata, which are not as a rule accompanied by desquama- 
tion. The genera] term dermatitis would be a more appropriate 
name, in my opinion, than erythema for the pellagrous eruption.' 

There are many reasons why the term dermatitis would be more 

appropriate. One of these is. as above mentioned, that only a 
few eases are true erythemata and it is certain that the skin 
affection of the vulva, the perineal region, the inner surfaces of 
the thighs, and even more rarely the scalp could not even loosely 
be classified as erythemata. 

It is largely to the American observers that the division of 
pellagrous skin lesions into two great groups is due. These are 
the " wet " and the " dry." After a varying interval of time 
there is superimposed on the erythema the formation of blebs, 
which neither in form, appearance, nor size possess any features 
peculiar to pellagra. Again we can see a marked similarity to 
solar erythema. I have seen many a ense of sunburn occurring 
in the early summer in a boy who has removed his shoes and 
stockings for the first time for the summer. Merk says that 
these blebs are the clinical means of discharging into the upper 

1 Fox, H., " Personal Observation on the Skin Symptoms of Pellagra." Med- 
ical Record, Feb. 5, 1910. 



SKIN MANIFESTATIONS 



187 



layers of the corium and epidermis an abnormally increased 
amount of Saftzufuhr and that the lesion takes on the form 
which is occasionally found in erythema exudativum of Hebra. 




Fig. 22. — Foot and Leg of the Patient whose Remaining Lesions are seen 

in Figs. 23 and 24. 



The seat of these blebs is usually the backs of the hands, less 
frequently the neck, and in some of my cases in children the 
legs and feet. The bleb is composed of only one chamber, that 
is, there are no partitions separating it into subdivisions. Usually 
the contents of the bleb fully occupies the bleb space and does 



188 



A TREATISE ON PELLAGRA 



not leave a flaccid condition which is sometimes seen in pemphi- 
gus. The contents of these blebs is at first, at least, sterile. 
I have frequently attempted on the various media to grow a cul- 
ture from this serum, but my efforts were always fruitless. 
It is not infrequent that the contents of the bleb becomes con- 




Fig. 23. — Dry Exfoliating Erythematous Process on Backs of Hands. This 
patient was affected with malaria — tertian and quartan combination. 



taminated from the outside with a resulting- pus formation which 
amounts to the conversion of the bleb into an abscess. In such 
conditions the underlying skin and that immediately adjacent to 
it becomes edematous and inflamed and the lymph glands also 
share in the inflammatory process. This secondary process is 
not peculiar to pellagra, but is solely attributable to the secondary 
infection. There naturally results a rise of temperature (see 
Chart I), which accounts for many of the supposed febrile 



SKIN MANIFESTATIONS 189 

cases of pellagra. With the rupture of these blebs containing 
a sero-purulent fluid crusting results. These crusts have a yellow- 
ish green color and, according to Merk, beneath them the epi- 
dermis repairs itself and finally assumes the spotted appearance 
seen in those cases in which the erythematous process did not go 
on to pus formation. He further states that in other cases the 
damaged corium and epithelial layer become transformed into 




Fig. 24. — Photograph of Same Case Represented in Figs. 22 and 23. Taken 
immediately after death. Part of a pellagra universalis. 

a granulating wound. This is illustrated by the foot lesion seen 
in Fig. 22. I have never seen this class of cases give rise 
to such conditions as erysipelas or sepsis. Furthermore, the 
glandular involvement in these cases of mixed infection never 
goes on to suppuration. The skin between the blebs is seldom 
normal. The bleb merely arises from a portion of the erythema- 
tous surface, but Merk mentions the possibility of the whole 
of a Casal collar being transformed into a single bleb, to which 
condition is given the name pemphigus pellagrosus. In those 
cases in which the blebs do not become secondarily infected there 
is a gradual drying up and the surface becomes transformed 
into a fine crust, beneath which the horny layer may in time 
regenerate itself. Often the contents of the bleb is lost by 
mechanical rupture ; in such cases the raw and bleeding areas 
uncovered by skin present the appearance of extensive burns. 
When, added to this, the patient is maniacal, as often happens, 
it is very difficult to keep these affected parts protected by any 



190 A TREATISE ON PELLAGRA 

sort of dressing and consequently the wounds bleed and the 
whole picture of blood and scabs, added to the general condition 
of the patient, is unequalled in medicine for its loathsomeness. 
The most revolting idea which we may conceive of Biblical 
leprosy cannot compare to the horrors of this form of pellagra. 
This type of case has caused the discharge in disgrace of more 
than one faithful attendant of our insane institutions. The 
reason for this is the fact that after the rupture of the bleb the 
skin strongly resembles a burn, and this led to the presumption 
that the attendant had been responsible through carelessness in 
giving a bath with too hot water. There are many pathetic ex- 
amples of this. 

Merk says that a few days after the appearance of the ery- 
thema the surface of the horny layer is found t<> contain many 
small fissures, which at first are confined to this layer but later 
reach the corium. This condition, like the bleb formation, does 
not occur in every locality where the erythema is found. The 
location is the backs of the feet and hands. Like the blebs they 
will heal gradually without leaving any traces if infection does 
not occur. In the event of the occurrence of infection a granu- 
lating wound results, followed by cicatrication. These rhagades 
or fissures are not infrequently combined with blebs in the same 
location. Many of the exudative lesions with piled-up crusts 
have resulted from these fissures in the skin and explain the 
occurrence of " wet " lesions without the occurrence of a pre- 
existing bleb formation. Often the amount of exudation in such 
cases is extreme. In maniacal patients these crusts are apt to be 
rubbed off, leaving a raw surface which would suggest the proba- 
bility of a preceding bullous condition. 

Merk also mentions the occurrence of pustules on the hands 
and occasionally on the feet. These pustules are said to vary 
in size from a millet seed to a pea. In some cases a coalescence 
of these pustules occurs. They may occur on the wrists, but 
seldom on the fingers. Xot infrequently this occurrence is said 
to complicate the erythema, which may also have been aggra- 
vated by the presence of blebs and rhagades. The resulting dis- 



SKIN MANIFESTATIONS 



191 



figurement is much increased. The erythematous redness which 
has usually at this stage begun to subside assumes a red color 
again as a result of the inflammatory process. The hands may be 
considerably increased in size by the pus and crusts as well as 
by the inflammatory swelling. The corium is made bare by the 
process. I have never encountered this condition, but W. F. 
Hargrove of Kinston, North Carolina, has told me of a re- 




Fig. 25. 



Pellagrous Lesions of the Hands. (Reproduced by courtesy of 
Dr. J. J. Watson.) 



markable case of his which might be put in this group. The 
patient was taken sick on the sixth of April with an eruption 
like chicken pox, lasting about six weeks and extending over 
the whole body surface. This eruption was more marked on the 
feet, hands, and face. There was some swelling of the wrists, 
knees, and ankle joints and a persistent stomatitis, together with 
a gastroenteritis. She had several hemorrhages from the bowels, 
two of which were quite severe. Diarrhea was always present. 
Her mind was clear until the termination of the disease in death, 



192 A TREATISE ON PELLAGRA 

but there was noted that characteristic retardation in replying' 
to questions. There were enough symptoms to make the diagnosis 
reasonably clear, but the skin lesions were most atypical. It 
was thought probable that the initial erythema had been present 
but had faded before she came under observation. I have never 
seen a pustule in pellagra, except when it was a bleb that had 
suppurated. Scheube says that the skin becomes red and swollen, 
causing the patient to suffer from the tension, as well as the 
itching and burning. The blebs and pustules dry up and crusts 
form. This is followed by a desquamation of the epidermis in 
large patches after a few weeks' duration of the erythematous 
process. Marie says that occasionally the drying up does not 
occur, but there develops an edema, followed by bulla?, pustules, 
and sometimes by gangrene. This is his conception of the " wet " 
form of the skin lesion. He further says that prior to the recog- 
nition of pellagra in the United States such cases were often 
called dermatitis exfoliativa as well as other similar skin diseases. 
It was stated above that between the blebs the skin was affected 
with an erythematous lesion and that these blebs arose from an 
erythematous base. This is not the experience of all. Some 
writers say that the skin between the blebs is normal. My own 
experience has been that the two great varieties, the so-called 
" wet " and " dry " forms, begin alike and do not separate until 
after the erythema has existed for some time. 
Hyde 1 describes the "dry" lesion thus: 

" The hue of the exanthem differs according to the color scheme 
of the subject and the length of time during which it existed. 
At first the color is a. dull red, which has been likened to the 
appearance of the skin after common sunburn; yet it is rare 
that the pinkish hue produced by the rays of the sun in the 
skin of a blonde subject is precisely imitated. The pellagrous 
erythema at the outset, generally fading temporarily under pres- 
sure, is more reddish than pinkish, displayed at times with dis- 

1 Hyde, James Nevin, " Pellagra and Some of its Problems." Amer. Jour. 
Med. Sciences, Jan., 1910. 



SKIN MANIFESTATIONS 193 

creet macules which speedily fuse and produce, on the backs of 
the hands for example, a uniformly smooth, reddened, and dis- 
tinctly outlined area, suggesting, when the cuffs have definitely 
limited the efflorescence above, the appearance of a glove cover- 
ing the back of the hand. In the milder cases the macular lesions 
may fade without producing the ' mask ' effect ; more commonly 
the eruption persists to a complete involvement of the areas ex- 
posed to the light. As the evolution of the erythema advances, 
the color deepens, refuses to disappear under pressure, and at 
its height attains a reddish-brown, chocolate, or plum-colored 
shade, described as ' livid bluish,' a tint at times suggestive of 
sepia. The first eruptive symptoms may disapj^ear in a fortnight 
with epidermic exfoliation in light flakes, leaving behind a pig- 
mentation differing according to the severity of the precedent 
engorgement." 

In the same article Hyde says further: 

" In most of the first attacks the eruptive phenomena facie in a 
fortnight, leaving the skin pigmented, roughened, and, in the case 
of many of the poorer class not under hygienic management, be- 
grimed with dirt. Many, indeed, of the American patients have 
a recrudescence of the exanthem in the autumn, some under our 
observation suffering even from repeated attacks in one season; 
while the type cases of Italian writers undergo a relighting of 
the morbid process in the skin, only at the succeeding season of 
spring (second stage), when possibly, without the production of 
as vivid an exanthem as at the first, the skin again becomes dull 
reddish in hue, is more deeply infiltrated and, when the exacer- 
bation passes, in cases in which the hands are involved, leaves 
these organs covered with a seamed, rugous, and irregularly 
roughened epidermis, which has given pellagra its distinctive 
title." 

The pigmentation of the erythematous areas has been empha- 
sized from the earliest writing and forms one of the most im- 
portant characteristics. The red color of the erythema gradually 







Fig. 26. — Note Deep Pigmentation which is More Common in Italy than in 
the Southern States. (Reproduced through the courtesy of the Illinois State 
Board of Health, Dr. J. A. Egan, Secretary.) 

194 









SKIN MANIFESTATIONS 195 

deepens and takes on a brownish tint until finally all semblance 
of the original erythema is lost. With this gradual change of 
color of the affected part there occurs also an exfoliation so that 
there is left an appearance suggestive in the photograph of leuko- 
derma, the contrast being between the fresh skin after the shed- 
ding of the affected skin and the brownish areas from which 
the affected skin has not yet been exfoliated. This is seen in 
Fig. 23. It has always seemed to me that this pigmentation 
has been exaggerated, due, doubtless, to the fact that most of our 
cases have been of a more acute character than the Italian cases. 
It is always noted that the erythema clears up from the center 
to the periphery, leaving a brownish " hyperkeratotic " border 
which is often only a line of light brown color, defining the limit 
of the previously existing lesion. This line is readily overlooked, 
even by a careful observer, but when discovered is of the greatest 
importance from a diagnostic standpoint. Many of our indefinite 
cases with a history of diarrhea, stomatitis, mental depression, 
and emaciation were cleared up by the finding of this line. It 
is especially clearly marked on the neck and the forearm, — those 
situations where the lesions are well defined. 

After exfoliation the skin is soft and velvety, suggesting that 
of a new-born infant. But with the yearly recurrences of the 
lesion on the same situation this softness is gradually replaced 
by a roughening of the skin. After several yearly recurrences 
of this process the skin atrophies and the tendons are seen stand- 
ing out distinctly through the thinned-out skin. 

In some cases the desquamation occurs in a very different 
manner, which cannot be said to be characteristic: there is a 
sort of furfuraceous process, which can readily be confused with 
other skin conditions, unless the general symptoms are taken into 
consideration. In such cases pigmentation does not play such 
an important part. 

Hyde mentioned the recurrences of the erythema at short 
intervals. This has been especially emphasized in our experience. 
I have seen evidences on a forearm of at least four distinct attacks. 
The first attack involved an area greater than the second, so that 



196 A TREATISE ON PELLAGRA 

there is a space between the first and second, as well as a difference 
in color. The second area is larger than the third in same man- 
ner, and the color of the third is not so deep as the second. The 
final appearance suggests the arrangement of the layers of a shell. 
This condition is somewhat depicted in Fig. 14. • Each of these 
lamellse represent an attack of erythema, and for some reason the 
size of the lamellae differ in each case, giving this peculiar over- 
lapping appearance. 

The occurrence of a hemorrhagic form of pellagra is reported 
by Strombio, Majocchi, Babes, and Sion, but such a case did 
not occur in my series. The first interest in this matter was 
shown in a discussion of the differentiation of pellagra and scor- 
butus. Merk says that the hemorrhagic flecks seen in the latter 
disease are very different from the hemorrhagic areas seen in 
pellagra. The difference is also in location, form, manner of 
appearance, their continuance, and in the accompanying condi- 
tions. Majocchi distinguished pellagra hemorrhagica from pur- 
pura. " In purpura the points of predeliction are very different 
from the common seats of pellagra. He said that hemorrhages 
in the outer mucous membranes in this form were not rare, through 
which a confusion with pupura is sometimes caused. Even a 
true intestinal hemorrhage may occur in pellagra. In this con- 
nection it should be added that there have occurred fatal intestinal 
hemorrhages in pellagra without any possible confusion with pur- 
pura. Von Scoccia in his sketch of Majocchi's lectures distin- 
guishes pellagra from purpura by the occurrence in the former 
of the erythema with subsequent pigmentation and desquamation, 
together with the points of predeliction shown by pellagra. 

As a general rule hemorrhagic processes in skin diseases 
point to a much more serious condition than in cases without 
them. According to Strombio, pellagra is no exception to this 
rule. 

Merk J in an earlier publication than the one which has been 

1 Merk, Verhandl. der Gesellsch. deutsch. Naturf. u. Aerzte Versammlung. 
77, 1905, and also a translation of the same in " Pellagra, A Precis " (revised 
edition), by C. H. Lavinder, U. S. Public Health Bulletin, No. 48. 



SKIN MANIFESTATIONS 



197 



so frequently referred to summarizes the characteristics of the 
erythema : 

This eruption is an erythema in a dermatologic sense, which 
can be compared to erythema exudativam (Hebra), as well as 




Fig. 27. — Extensive Areas of Involvement of the Posterior Surfaces of 
the Hands, Forearms, and Arms and a Faint Casal Collar. (Photographed 
and seen through the courtesy of Dr. J. B. Cranmer, Wilmington, N. C.) 



to certain toxic, endemic erythemata like lupine disease in animals 
(fagopyrismus) ; also to lathyrism and ergotism. 

The eruption appears suddenly, and its genesis is not neces- 
sarily connected with atmospheric or solar influences. 

Its limitations are peculiarly typical — sharp with red borders 



198 A TREATISE ON PELLAGRA 

— and as it develops it shows a more or less broad zone of scaling 
with a peculiar color. 

It is days and even weeks before the eruption reaches its height, 
and even a longer time is required for its retrogression. At first 
there is a loss of the rosy border, then a gradual fading of the 
center, while the scaly, crusty zone remains for a long time the 
seat of the retrogressive process. The changes in the central zone 
vary with location, but are always characteristic of an erythema. 

By its external characteristics the erythema is strongly allied 
to the so-called hyperkeratosis. But it may show enormous ex- 
udation, especially on the backs of the hands. 

The erythema is almost always remarkably symmetrical and 
shows certain points of predeliction, — first on the backs of the 
hands ("glove"), more rarely the upper surfaces of the feet 
(" boot "), still more rarely the face (" mask "), and finally the 
neck (" Casal's neck-band" and " Casal's cravat") ; in the sec- 
ond place, the female genitalia and perineal region. It is also 
seen in asymmetrical, isolated situations, as elbows, knees, and 
axillary folds. 

Some time after its appearance the erythema shows the typical, 
dirty gray-brown color of changes peculiar to hyperkeratosis. At 
the same time the bright red of the erythema may be seen through 
this, and gives to the whole a kind of bronzing, which is especially 
sharp during the retrogression of the process. 

It appears as a rule once annually and this time is usually the 
spring. It recurs the following year, and finally leads to atrophic 
changes, especially on the backs of the hands. 

The time of the appearance of the skin eruption of pellagra in 
the southern states is a very variable thing. In my opinion the 
character of the weather will determine an early or late outbreak 
of the erythema. As a rule, however, the appearance in the 
southern states is later than in southern Europe. Many more 
of my own cases appear in May and June than in April and 
May. It is no unusual thing for the erythema not to appear 
until late summer and even well into the fall. Recurrences in the 
fall after an attack of the erythema in the spring frequently occur, 



SKIN MANIFESTATIONS 199 

but are not the rule. There are many cases, as mentioned above, 
in which repeated exacerbations of the erythema occur on the old 
lesion before healing is complete. Again, almost immediately 
after the subsidence of one attack a fresh outbreak occurs. In 
many instances these exacerbations amount merely to a reddening 
of the skin with a subsequent tendency for pigmentation to 
occur. Often these attacks are so trivial as not to be followed by 
desquamation. 

There has been a considerable difference of opinion regarding 
the pathologic changes produced in the skin in pellagra. This is 
explained on the ground that the changes are subject to great 
variations just as are the clinical manifestations produced by 
them. Very little experimental work has been done on this subject, 
as the skin changes are not distinctive in themselves of the disease, 
being merely the changes produced in many of the dermatitides 
and erythemata. Merk himself had never had an opportunity to 
study the skin microscopically, and this is the experience of most 
pellagrologers, due to the fact that pellagrins do not die in the 
eruptive stage, but usually after the erythema has subsided. In 
the acute cases which have died under my care the changes were 
not distinctive, because sufficient time had not elapsed for the im- 
pression of the disease to be made on the structure of the skin. 
Griffini made one of the most important studies of this problem. 
He examined the skin of three cases. The skin was compared 
with the skin of an old man. The skin of the first patient was in 
the desquamative stage and the patient was twenty-three years of 
age. The second specimen was anemic and the third was in the 
atrophic stage. In the first case he found the horny layer hyper- 
trophic, the scaling was very profuse and the rete Malpighii showed 
a decided tendency to hyperplasia. In the second specimen the 
blood vessels of the papillae and deeper layers were sclerosed. In 
the third case there was sclerosis of the vessels of the deeper 
layers, though in less degree; this same condition was also found 
in the connective tissue of the corium. He also found an atrophy 
of the horny layer. The rete Malpighii of these patients showed 
slight hyperplasia. The sweat glands, hair follicles, and sebaceous 



200 A TREATISE ON PELLAGRA 

glands were normal. Raymond's results were different. He had 
studied the skin of an old pellagrin and he recognized only an 
atrophy of the skin, which is the inevitable result of repetitions 
of the pellagrous process. He found essentially a thinning of the 
epidermis and a disappearance of papillce. The lamellae were 
separated by crevices of different length and breadth. The horny 
layer as a whole was thickened. There was an abundant scaling 
and especially emphasized was the hyperkeratotic process. The 
stratum granulosum was composed of small, elongated cells, which 
did not appear to contain more elcidin than normal. The rete 
was atrophic and the number and size of the colls were lessened. 
In many instances the nuclei of the cells were wanting. The 
papillae had entirely disappeared. In the corium were vascular 
tufts, which stood in conspicuous contrast with the atrophy of 
the epidermis. The hair follicles, sweat glands, and nerves were 
unaffected. As the skin changes progress he connected the de- 
cided hyperkeratosis with atrophy of the rete. 

Babes and Sion, according to Merk, examined the skin in dif- 
ferent stages. They found in different stages hypertrophy or 
atrophy. In the earlier stages the epidermis was thickened or 
thinned, but in the later stages the change was altogether one 
of atrophy. During the stage of desquamation the epidermis was 
thickened. The rete Malpighii may be thickened or thinned. 
During desquamation different layers are well defined, both by 
color reaction and by structure. This is seen in the stratum 
corneum where a large meshed network occupies the greater part. 
Besides hyperemia Babes and Sion found in the skin definite 
but slight serum transudation, with few leucocytes and a definite 
metachromatic, homogeneous, and diffuse mass (probably albumi- 
nates). There were also found sweat glands rich in cells and 
metachromatic granulations. Nothing significant was found in 
the nerves. The changes found in the stage of desquamation and 
pigmentation are much more important, according to these ob- 
servers. There is here seen the proliferation of the epithelium, 
the separate, well-differentiated homogeneous layers being formed 
of dense or loose material. The inner epithelial layers contain 



SKIN MANIFESTATIONS 201 

much pigment of a yellow color. The papillae in the process of 
cell proliferation are included and are provided with abundant 
plasma cells. The sweat glands are proliferated and the enlarged 
sebaceous glands often contain large colonies of small diplo- 
bacteria, and in this location granulation tissue, either diffuse 
or in foci, is placed. In this same place the plasma and endo- 
thelial cells are enlarged. The thickening of the skin is caused 
by a peculiar underlying tissue composed partly of hyaline ma- 
terial, which is wavy and dense, with broken fibers. There are 
also found round masses composed in part of exudate and in part 
of degenerated elastic tissue. In this tissue, which shows in part 
a reaction for elastic fibers by the Weigert stain and in which, 
in part, the straining properties with eosin and hematoxylon are 
quite feeble, there appears in the light blue mass many thick rods, 
which suggest bacilli stained feebly with the aniline stains. There 
is also a peculiar condition of irritation and exudation, which in 
the beginning, at least, can be comj)ared to an erythema from the 
eating of certain food in individuals who are susceptible. Later 
a peculiar process appears, which is sclerotic and desquamative 
and which injures the function of the skin. 

Merk remarks that he would have wished to look further into 
these findings of Babes and Sion, 1 especially into a consideration 
of the stages in which the various changes were found in order to 
study step by step the various changes which finally lead up to 
atrophy and pigmentation. He says in substance : 

" Experimental examination of the normal human skin has 
taught me that the processes in the horny layer, designated partly 
as hyperkeratosis and partly as parakeratosis, could be due to the 
normal processes of this layer. From this standpoint it would 
be interesting to be able to follow out the processes which have 
resulted in the degeneration and desquamation of the horny layers, 
and in which histologic change the red color has its origin ; the 
bleb formation, too, might be accounted for in the same study. 
The only matter about which I am positive is that the exfoliated 

1 Babes and Sion in " Spec. Pathologie u. Therapie von Nothnagel," 1901. 



202 A TREATISE ON PELLAGRA 

cells of the horny layers do not take the nuclear stain. The con- 
dition of that portion containing connective tissue is not men- 
tioned satisfactorily. Raymond found no changes in this part, 
while Babes and Sion found quite notable changes, especially in 
the elastic fibers." 

The American edition 1 of Marie's work summarizes the study 
of Griffini thus: " . . . marked atrophy of the stratum corneum, 
copious desquamation, active reproduction in the Malpighian reti- 
culum and marked sclerosis of the vessels of the papillary layer and 
the derma." 

The skin manifestations of pellagra will ever remain the most 
important features of the disease from the standpoint of diagnosis 
until the discovery of some such blood test as the Wasserman 
or Noguchi tests in syphilis. In the meanwhile, as previously 
stated, the diagnosis must hinge on the skin symptoms and in 
their absence, or in the event of only atypical manifestations, the 
diagnosis should never be made. As formerly stated, the character 
of the skin lesion per se is of the smallest consequence, but even 
this rule has its exceptions. The photograph designated Fig. 30 
well illustrates the importance of this point. This case was 
properly suspected as pellagra because of the location on a por- 
tion of the body exposed to the light and air. The most important 
feature of the skin manifestations is symmetry; after that the 
location of the skin lesion, chiefly on the exposed parts ; finally, 
the well-defined seasonal variations. 

Merk, after a consideration of all the conditions which in 
the past had been confused, with pellagra, concludes that only the 
following skin conditions offer sufficient points of resemblance 
to cause any real difficulty: solar erythema, a strange form of 
vitiligo, eczema, erythema exudativum multiforme (Hebra), and 
erythema polymorphe of the author. 

It has always been recognized that the sun played a conspicuous 
part in the production of pellagrous erythema, but in itself could 

1 " La Pellagra," A. Marie. Translation by Lavinder and Babcoek. Colum- 
bia, S. C, 1910. 




Fig. 28. — Boy 



v ~ Z ^ the Baptist Orphanage. (Reproduced by the courtesy of the 
Tennessee Board of Health, Dr. Wm. Krauss, Chairman Pellagra Commission ) 



203 



204 A TREATISE ON PELLAGRA 

never produce it. We can hardly agree with Landouzy and 
Bouchard in their declaration : " Supprimez le soleil, et vous 
supprimerez la pellagre." The solar theory received a serious 
blow when it was conclusively shown by Merk and others that 
such regions as perineal and perigenital could be the seats of 
the true pellagrous erythema. There is hardly a portion of the 
body surface which has not at some time or another been the seat of 
the disease, but as repeatedly emphasized this does not justify 
the diagnosis unless there also occurs in certain of the exposed 
portions of the skin the symmetrical erythema. Merk says that 
the areas of sunburn or weathered skin are much more extensive 
than the areas of pellagrous erythema. In this I cannot agree. 
He also remarks that the experiment of Gherardini in which 
holes were cut in the garment of a pellagrin and then the patient 
was exposed to the sun's rays, with the result that areas of ery- 
thema occurred, conforming to the holes in the garments, were not 
conclusive because the same thing would occur if a cachectic 
patient or an alcoholic and even a healthy individual were ex- 
posed to the same thing. Merk further states that in solar ery- 
thema the symptoms follow such an exposure and when the part 
is exposed to the air relief is produced. In pellagra exposure to 
the air produces a burning which first attracts the attention of 
the patient to the condition. Again, pellagrous erythema is strictly 
confined to exposed parts of the body. The differences in color 
have been referred to on a previous page. 

There is a condition seen in men and sometimes in women 
when they are much exposed to the weather, which resembles 
that form of chronic pellagra with the dry scaling of the skin. 
I have noticed it especially in such occupations as oyster shucking 
and among fishermen. It is readily distinguished from pellagra 
by the absence of the definite line of demarcation between the 
normal and diseased skin and by the absence of such symptoms 
as stomatitis, diarrhea, nervous disturbances, and emaciation. 

The confusion of pellagra with vitiligo is a more important 
matter than would appear on first thought. Could the observer 
see the erythema of pellagra from the beginning this confusion 



SKIN MANIFESTATIONS 205 

would not occur, but, unfortunately, it often happens that the 
first observation is made during the period of desquamation when 
many an accomplished dermatologist has made the mistake. Merk 
says he has observed this condition in women and children, and 
that it is the form of vitiligo mentioned in the writings of Fox 
and Darier. Owing to the pigmentary disturbances there is a 
contrast in the color of the skin of exposed parts with other parts. 
In the cold months it is said that the pigment is normal, but in 
the spring there is a decrease of pigment, due to the contact of air 
with the exposed portions of the skin, and as a result that portion 
with a lessened amount of pigment has a fresh rose color in sharp 
contrast to the adjacent over-pigmented skin. This condition often 
occurs symmetrically on the backs of the hands. Such an appear- 
ance is said to resemble strongly the skin of the neck after the 
subsidence of a pemphigus pellagrosus. Again in this condition 
an investigation of the general condition of the patient is often 
necessary to dispel the doubt. 

The one skin condition which I most often see, because the 
patient or his physician suspects pellagra, is eczema. Only a 
few days ago a clergyman consulted me because of a symmetrically 
placed squamous eczema on the anterior surfaces of his thighs. 
Merk pertinently remarks that an error of this kind would be 
possible only if the backs of the hands happened to be sym- 
metrically affected; that such an eczema would have to run its 
course in a few weeks and subside without therapeutic aid; that 
the form would have to be the squamous, with a sharp line of 
demarcation, with no itching of any note, and an absence of 
a suggestion of a vesicular stage. He says further that such a 
form would be theoretically scarcely conceivable, but that practi- 
cally there is found one or more of these symptoms or even a 
series of them, though only a very superficial glance would lead 
to error. Probably the most important point of differentiation 
would be the brownish pigmentation, which is so often charac- 
teristic of pellagra. 

Merk finds more similarity to erythema exudativum multi- 
forme (Hebra) than to any other condition of the skin. He 



206 A TREATISE ON PELLAGRA 

says that the diagnosis cannot be made by a glance, but that the 
whole course of the disease must be carefully considered. The 
most important point in this question is the locality of Hebra's 
disease. He gave as the localities affected the backs of the hands 
and the feet, and in severe cases also the forearm, leg, arm, upper 
portion of the thighs, and almost invariably the trunk, and the 
face; it is never lacking on the backs of the hands where the 
first efflorescence usually occurs. It will be seen how many 
points of similarity there are to pellagra. Hebra's pupil, Kaposi, 
added to the description of this disease by including herpes iris 
and circinata in the consideration and called the whole group 
erythema polymorphs Kaposi taught that changes can occur in 
the mouth and throat quite similar to the changes produced by 
pellagra on these same mucous membranes. He also stated that 
the vulvo-vaginal and urethral mucous membrane might be 
affected. Besides all this, both Hebra and Kaposi mention the 
fact of seasonal variations. It is highly probable that some cases 
of pellagra have been diagnosed erythema multiforme, especially 
when pellagra is discovered in one who does not eat corn. With 
care and a consideration of all features of the case there is but 
small chance of error. 

Acrodynia is a disease regarded by many dermatologists as 
quite similar to pellagra. It is ushered in by symptoms of anor- 
exia, nausea, vomiting, and diarrhea. The face, hands, and feet 
are found to be swollen, the conjunctiva? injected, and the nervous 
system affected. These disorders of the nervous system are many 
and varied. Among them are prickling and burning sensations; 
at first marked hyperesthesia of the extremities followed by anes- 
thesia. Often there is a complaint of severe pain in the extremi- 
ties. Early in the disease the eruption appears and presents 
erythematous spots primarily on the hands and feet, but especially 
on the palms and soles. It spreads upward on the arms and legs 
and sometimes involves the trunk. The skin affected is thickened 
and of a brown color, and finally desquamation occurs. Black 
pigmentation may follow. It runs its course in a few weeks. 
In some cases pareses and toxic spasms follow. It is an obscure 



SKIN MANIFESTATIONS 207 

disease, thought by many to be a toxemia affecting chiefly the 
nervous centers. It has been thought to resemble chronic arsenical 
poisoning. Usually the prognosis is favorable. I had no knowl- 
edge of this disease until after beginning the study of pellagra, and 
while I cannot, therefore, speak authoritatively, I am reasonably 
confident that several patients have consulted me, suspecting that 
their trouble was pellagra, when it was really acrodynia. My 
chief basis for this opinion was the occurrence of the skin lesions 
on the soles of the feet and the palms of the hands. 

Much is said in the literature of pseudo-pellagra, but there is 
no occasion to consider it here in the differentiation of the skin 
lesions from those of pellagra, because in my opinion pseudo- 
pellagra is a misnomer coined for the purpose of relieving the 
situation for those who believe that the only cause of pellagra is 
diseased maize. Clinically a study of this condition made famous 
by the writings of Billod offers no points of difference from the 
true disease. Manson expresses himself thus : " The disease is 
pellagra when it fits in with the orthodox theory and when it can 
be connected in any way with maize, but when this is not possible, 
the disease becomes pseudo-pellagra." Fortunately, in this 
country we are not so tied down by tradition to refuse to make 
a diagnosis, because the etiological factor cannot be accounted for, 
— that is, even the most ardent of the American zeists will grant 
such a diagnosis with the clinical evidence before him. 




CHAPTER V 

THE DIGESTIVE DISTURBANCES 

The first indications of pellagra are found almost invariably 
in the gastrointestinal tract. It will be shown in the next chap- 
ter that pellagra may occur without the manifestation of any 
symptoms referable to the nervous system, and again it will be 
shown that in some other cases nervous and mental symptoms 
may usher in the initial attack, but pellagra without an impression 
on the digestive apparatus has never occurred in my experience. 
It would be very questionable in my mind if a diagnosis without 
these manifestations would be justified. In an experience with 
four hundred cases I have never seen a single case of this kind. It 
is much more frequently necessary to consider the probability of 
pellagra without skin manifestations, and as previously stated, at 
this time, this possibility is not admitted. Allbutt says that dys- 
pepsia is the first symptom to follow the invasion of the pellagra 
poison. So impressed was Strombio, the elder, with the constancy 
of these digestive disturbances that he concluded that the origin 
of the disease was in the digestive apparatus. As stated, the occur- 
rence of a pellagrous skin lesion without digestive disturbances is 
unknown in my experience, but should it occur the other manifes- 
tations would have to be of a very typical character before the diag- 
nosis would be justified. It is much wiser for American students 
to learn that the disease cannot be diagnosed unless there are present 
skin, gastrointestinal, and nervous symptoms. In this way error 
may be avoided and, on the other hand, the patient will be pro- 
tected because pellagra will never exist very long without the mani- 
festation of the triad of symptoms. 

Among the digestive disturbances probably the most unvarying 
in the constancy of its presence is the stomatitis. When we know 



THE DIGESTIVE DISTURBANCES 209 

more of the so-called " pellagra-sine-pellagra " it is possible that 
stomatitis may be shown to be a more constant symptom than the 
erythema. At the present time it should be placed second in the 
list of symptoms. 

Tn the series of one hundred cases of the pellagra report of the 
Illinois State Board of Health it will be noted that mouth symp- 
toms occurred in seventy-two of the cases, hence the percentage 
without was twenty-eight. This is quite different from my own 
experience and shows the variation of pellagra in different locali- 
ties. In my series in only five per cent of the cases was stomatitis 
absent. It is very probable that in a large portion of those cases 
reported without stomatitis this symptom would have been noted 
had the whole course of the disease been observed. Again, in many 
cases the mouth symptoms are often as trivial as are the skin symp- 
toms in certain instances mentioned previously, and as the skin 
lesions are often not noted by even the patient so, also, is the case 
with the mouth symptoms. In many instances to the question 
regarding the sore mouth the patient replies in the negative, but 
a careful examination will reveal the presence of a definite in- 
flammation. From this very mild type of stomatitis there are 
all gradations up to a severe general inflammation of the whole 
mucous membrane of the mouth and the tongue. In our earlier 
experience we often considered this condition of the mouth to be 
due to mercurial ptyalism, which is very common in the South, 
owing to the frequency of the free use of calomel and blue mass. 
To distinguish between the two conditions is often impossible. 

The sponginess of the gums and the readiness with which they 
bleed gave rise in the past to the name " Alpine scurvy." 

The Changes undergone by the tongue and mouth are quite 
marked. Harris says that the tongue epithelium shows much the 
same changes as are observed in the epiderm in the affected por- 
tions of the skin. Later the epithelial cells are exfoliated around 
the edge of the tongue, and this process, in some instances, is con- 
tinued until the whole structure of the tongue becomes bare. But 
even in the case of the apparently bare tongue on microscopic 
examination a thin epithelial layer may still be demonstrated. 



210 A TREATISE ON PELLAGRA 

Furrows are very abundant on the dorsum of the tongue and the 
redness is general and usually uniform. Ulceration may occur 
as a late change. This ulceration begins usually on the edges and 
later may appear on any portion of the tongue surface as well as 
on the buccal mucous membrane. These changes Harris considers 
to be identical in most particulars with the changes in the skin. 

Sometimes small congested areas are found scattered irregularly 
throughout the mouth. In these areas the mucous membrane has 
lost its smooth and brilliant appearance, and the absence of epithe- 
lium produces a dark red color. At first these areas are the size 
of a split pea. This condition has never attracted my attention 
and I do not regard it as particularly characteristic. About the 
labial commissure there occur ulcerated areas of a white color; 
these ulcerated spots are continued to the inner surface of the 
mouth so that the buccal ulcer is continuous with that of the skin. 
These ulcers of the buccal ' mucous membrane are spoken of by 
one writer as " hyperkeratotic streaks." The buccal mucous 
membrane may be the seat of a very acute inflammatory process 
which is characterized by redness, a loss of the brilliant tint for- 
merly seen, together with a roughening of the surface with super- 
ficial excoriations and white spots which are encased in mucus. 
There occasionally occurs vesiculation of the buccal mucous mem- 
brane. The tongue is the seat of the same kind of process which 
is especially marked along the edges. 

In the ordinary type of mild case there is nothing distinctive 
of the condition. The appearance is that of a general redness 
evenly distributed. Sometimes it suggests to the mind the appear- 
ance of the mouth in scarlet fever with the exception that that 
particular enlargement of the papillae which goes to make the 
" strawberry " tongue is wanting and the hue is more of a purple 
than a red. This redness is especially marked on the hard palate. 
Babcock has called attention to a peculiarity of the process when 
it involves this area of the hard palate: a tendency to form a 
definite line of demarcation of the process, the line being situated 
at the point in the mouth which marks the limit of an artificial 
plate for false teeth. I have repeatedly noted this line of de- 



THE DIGESTIVE DISTURBANCES 211 

marcation and it has been so definite in some cases that a casual 
glance would make one think that the patient was really wearing 
a plate. This occurrence is not constant and is wanting in more 
cases probably than it is present. 

In the more severe form of stomatitis the tongue is fiery red 
and may be edematous. The buccal mucous membrane is in- 
tensely inflamed. Ulcers may be found in any portion of the 
mouth. The secretion of saliva may be so intense that the patient 
cannot speak intelligibly because of the rapid filling up of the 
mouth. According to Zeller the inflammatory process may be so 
severe as to prevent the protrusion of the tongue and to interfere 
greatly with the taking of food. 

The denuded tongue is found to be smooth and glistening and 
from the color, which is a cardinal red, arose the term, cardinal 
tongue. Sandwith with equal accuracy calls it the bald tongue. 
Ulcers do not appear on the tongue until late in the course of the 
process, and I have observed many cases without any ulceration 
throughout the whole course of the disease. 

Babcock calls attention to small black or bluish black spots on 
the dorsum of the tongue. This appearance is especially noted 
in negro patients. Having this appearance ,in mind Lavinder 
gave this tongue the name " stipple tongue." 

The tongue in pellagra is either pointed and tremulous or it is 
large from inflammatory swelling and shows the indentations of 
the teeth. 

The salivary glands are often enlarged and tender ; this enlarge- 
ment of the glands and salivation gave rise to the confusion with 
mercurial ptyalism. The disagreeable odor in mercurial poison- 
ing is much more offensive than in the salivation of pellagra. 
Watson says that the acme of the stomatitis corresponds to the acme 
of the skin process. 

Usually the first symptom complained of is the sensation of 
heat in the mouth, throat, and stomach. Taste is impaired and 
there is marked anorexia. 

It is thought that these complaints of heat in the esophagus and 
stomach are part of a neurosis. I cannot deny that one of the 



212 A TREATISE ON PELLAGRA 

neurotic symptoms may be this complaint of burning, but, on the 
other hand, I know that the inflammatory process often extends 
downward involving a considerable portion of the esophagus. The 
redness extends throughout the pharynx as far as the eye can see, 
and a further examination will reveal the process in the esophagus. 
The tongue condition together with the intestinal symptoms in 
pellagra has given rise in some sections of the South to the idea 
that sprue is prevalent in that region. It is very probable 
that sprue does occur and this is one of the best reasons for hesi- 
tation in acknowledging the possibility of a pellagra-sine-pellagra, 
for the symptoms of sprue are almost identically those of pellagra 
without skin manifestations. The matter is so important that the 
following from Manson's account of sprue in Allbutt's " System " 
is given : * 

" Tenderness and often great soreness of the tongue, buccal 
mucous membrane, fauces, and sometimes of the gullet, depending 
on a complexity of surface lesions including (a) denudation of the 
epithelium of the mucous membrane generally; (b) the formation 
of minute herpes-like vesicles, single or in groups, with an in- 
flamed areola, which quickly rupture, leaving (c) small, superficial 
but exquisitely tender, ashen-gray ulcers; (d) larger, inflamed, 
bare, slightly-eroded patches, smooth on the surface usually, or 
with a slight muco-purulent covering where in contact with the 
teeth — as when on the inside of the cheeks or lips ; often, when 
on the soft palate, they are markedly granular, probably from in- 
flamed follicles; (e) congestion and swelling of the fungiform 
papilla?, especially about the tip and edges of the tongue; (f) 
superficial cracks on the dorsum and edges of the tongue; (g) 
during complete remission of the acute symptoms, as happens occa- 
sionally in most cases, an atrophied state of the entire body of the 
tongue; this organ then appears pale and almost cartilaginous, 
with a smooth, glazed surface as if coated with varnish, and com- 
pletely denuded of papilla?. 

" The erosions referred to, sometimes amounting to superficial 

1 Manson, Sir Patrick, in Allbutt's " System of Medicine," III. 



THE DIGESTIVE DISTURBANCES 213 

ulceration and much sodden by the constant action of the saliva, 
are most frequently found under the tongue by the sides of the 
f renum, inside the lips and cheeks ; especially where in contact 
with the teeth, and on the soft palate. The vesiculations ending 
in the minute gray ulcers are commonest about the tip and edges 
of the tongue ; they come out in successive crops. Activity of both 
of these lesions is usually associated with increase of diarrhea. In 
severe cases what I would call the • psilotic ' condition of mucous 
membrane seems to extend through the entire length of the ali- 
mentary canal, affecting the pharynx, esophagus, the anus, and in 
women, even the vagina." 

It is not only in regard to the mouth symptoms that sprue must 
be considered in connection with pellagra ; there are many points 
of resemblance in all the alimentary manifestations of the two 
conditions. For myself I can find no satisfactory points of dis- 
tinction between sprue and pellagra without skin manifestations. 
In the Transactions of the Pan-American Medical Congress for 
1893 is found an article by Cuthbert Bowen entitled " Psilosis ( ? ) 
Pigmentosa," a disease described as occurring in Barbadoes which 
is not recognized as pellagra, but an inspecton of the illustra- 
tions makes such a diagnosis, in the light of our present knowl- 
edge, very plain. There is a splendid water color of the tongue 
in this condition and another of the tongue in " Indian sprue." 
The contrast is very striking and of great value in distinguishing 
the two conditions. In the tongue of the condition which we now 
recognize as pellagra the papillae are injected and four aphthous 
spots on the lateral edges are noted. This tongue is pointed and 
of a characteristic color, while that of sprue is of a much paler 
tint and is covered by furrows and ridges. This tongue is rep- 
resented as larger and rounded at the end instead of being pointed 
as in the pellagra illustration. Thin says that the salivation de- 
scribed in this Barbadoes condition, which I consider pellagra, 
does not occur in East Indian sprue. 

Some time ago I was interested in a consideration of the possi- 
bility of pellagra having existed in our insane institutions unrec- 



214 A TREATISE ON PELLAGRA 

ognized for some time. Through the courtesy of the late James 
McKee I was given much valuable information regarding the 
occurrence of a condition in the State Hospital for the Insane 
at Kaleigh, North Carolina. There was a condition there which 
was attended with the characteristic skin manifestations of pel- 
lagra and a stomatitis. Doctor McKee in describing the condition 
told me that it more nearly resembled stomatitis materna than any 
other condition with which he was familiar. 

There would be some reason for the confusion of the stomatitis 
of pellagra with the mouth condition of syphilis, especially when 
the pellagrous process has advanced to the ulcer formation. The 
differentiation is made bv the lack of the general diffuse redness 
seen in pellagra and the systemic manifestations. In the past, 
however, before it was known that pellagra could be found in this 
country, there was much stress laid on the mouth symptoms of 
cases that were really pellagra as pointing to a syphilitic condition. 

Eoussel considered loss of appetite, nausea, and gastric disturb- 
ances to be complications of pellagra, but dryness of the esophagus, 
dysphagia, and pyrosis the first symptoms of the disease. These 
gastric symptoms as well as cardialgia, hunger, diarrhea, and vom- 
iting he considered of nervous origin. Many patients suffer from 
great thirst while others abhor drink of any kind. Eructations 
and other symptoms of the so-called nervous indigestion are fre- 
quent. Usually the patient has been under the care of the physi- 
cian for a number of weeks suffering with vague and indefinite 
gastric symptoms before the appearance of the stomatitis and ery- 
thema. The gastralgia which occurs may sometimes be mistaken 
for the gastric crises of tabes dorsalis. Procopiu, according to 
Lavinder and Babcock, says it may cause gastric intolerance, and 
occurs in paroxysms having no relation with the taking of food. 
The fact that the hydrochloric acid of the stomach is diminished 
in pellagra is used as an argument that the sensation of burning 
in the stomach and esophagus is of purely nervous origin. Pro- 
copiu agrees in this view or thinks that if not due to the nervous 
influence it is brought about by a lesion of the mucosa of the part 
which is analogous to the erythema. It is said that sitophobia 



THE DIGESTIVE DISTURBANCES 215 

occurs frequently in pellagra, among the insane patients especially, 
but those who are mentally sound often manifest a great disgust 
for food, especially the meat foods and, according to Marie, po- 
lenta. Many patients have an inordinate appetite and will devour 
everything within their reach regardless of amount or kind. I 
have seen this symptom in its most exaggerated form, and again, 
I have seen patients starve themselves owing to the great disgust 
for any form of food. Marie * mentions the case of a pellagrous 
woman who exhibited this voracious appetite and who just before 
the onset of the terminal delirium left her house to avoid devour- 
ing her children. 

Lombroso, Filippi, and Roncoroni made gastric analyses of two 
pellagrins. The stomach was found practically empty, the first 
four hours after taking food and the second about two hours. 
The test meal consisted of a bowl of soup, eighty-five grams of 
meat, two hundred grams of bread, and one hundred grams of 
wine. Four tests were made in each case. Hydrochloric was 
found diminished and lactic acid frequently present. 

W. O. Nesbit 2 in a routine examination of the stomach con- 
tents of ten pellagrins found the following : 

In six cases there was a marked diminution in the acid factors 
of the gastric juice in the late stages of the disease. 

In five cases there was found an excess of mucus during the pel- 
lagrous periods. 

Six cases showed normal motility, while in three the test was 
not made. 

Four cases showed the presence of bile during severe vomiting 
periods. 

Xiles 3 in two hundred cases was able to find records of less 
than twenty cases in which vomiting occurred and concluded that 
it was rather an unusual condition. 

J. J. Watson writing of the gastric manifestations noted by 
him said : 



1 Lavinder and Babcock's translation of Marie's work. 

2 Nesbit, W. O., Trans. Nat. Pel. Cong., 1910. 

3 Niles, Gr. M., "Pellagra: An American Problem," 1912. 



216 A TREATISE ON PELLAGRA 

" Vomiting occasionally occurs, but is not a constant feature 
of the disease. When the disease is advanced dysphagia is com- 
plained of by some patients, and this may be accompanied by 
strangling when fluids are taken. 

" Marked gastric symptoms are in evidence in some cases. I 
have known a case of pellagra diagnosed as gastric cancer. The 
only abnormality detected by abdominal section was an exces- 
sive redness of the peritoneal coat of the stomach. After a few 
days the patient was rolled out into the sun and soon there ap- 
peared on her forehead and hands an intense erythema. This 
aroused suspicion, and two competent consultants were called in. 
From the history of repeated attacks of eruption and the picture 
presented by the patient, the diagnosis of pellagra was made and 
the subsequent course of the eruption (color, etc.), tongue, diar- 
rhea and depression, put the diagnosis beyond doubt. Hematemesis 
is sometimes seen." 

In a case of my own which will be detailed in the next chapter 
there occurred persistent vomiting, and the patient gave a history 
of having vomited half a pint of bright red blood with an absence 
of any other symptom of gastric ulcer. It should be said, how- 
ever, that this patient was an alcoholic and there were other symp- 
toms which suggested the probability of cirrhosis of the liver. In 
other cases I have noted persistent nausea and vomiting, but the 
percentage in my series of this condition was little more than two 
per cent so that I must agree with Niles that vomiting in pellagra 
is not a common symptom. 

The changes found in the stomach by Harris were dilatation of 
the walls in consequence of atrophy of the muscular coat. The 
mucosa was often pale. In some instances the surface in the 
pyloric region was quite red. 

It would be expected from the pathologic condition that there 
would be some catarrhal symptoms. Agostini, who studied the 
stomach very carefully, said that the marked " hypopepsy " which 
he found was due to a catarrhal condition. He also noted that 
motor and glandular insufficiency was well marked. It was 



THE DIGESTIVE DISTURBANCES 217 

further noted that in severe cases the deficiency in hydrochloric 
acid was more marked than in the mild cases and that in some 
cases it was entirely absent. As a natural result digestion was 
found to be greatly impaired, peptones were found deficient, and 
the catarrhal discharge facilitated the lactic and other fermenta- 
tions. Allbutt thought that to expect a means of diagnosis from 
analysis of the stomach contents would not be in order because 
by the time these changes had existed long enough to assume 
any definite character other more positive symptoms would have 
appeared to make the diagnosis a matter of no difficulty. 

In describing psilosis pigmentosa C. G. Manning speaks of the 
occurrence of light red petechia scattered throughout the wall 
of the stomach. He says that these petechias are the cause of 
the blood-stained vomitus and the melena ; that there occurs a 
slow but steady depletion from the intestinal tract as in anky- 
lostomiasis. The petechia? may be stellate from the presence of 
congested vessels leading to them. There can be no reasonable 
doubt that this disease, as mentioned on a previous page, is pel- 
lagra, but no other observer has described this condition. It 
would be a solution of the problem of how gastric hemorrhage can 
occur, as it certainly does in some cases, without other evidence 
of definite ulceration. 

In the series of one hundred cases reported by the State Board 
of Health of Illinois fifteen of the number had no diarrhea. This 
percentage is much higher than in the cases under my observation. 
This is probably another of the instances in which the disease is 
seen to vary with the locality. The same thing was illustrated in 
the consideration of stomatitis, in which instance it was seen that 
stomatitis did not occur in such a large percentage of the cases in 
Illinois as in the South. In my own experience there were a few 
instances of obstipation in place of the usual diarrhea, but such 
instances were isolated. It is very unusual that some time in the 
course of the disease this important symptom does not occur. 

Tuczek found in the intestinal tract attenuation of the wall in 
consequence of atrophy of the muscular coat, and hyperemia and 
ulceration of the lower portion of the large intestine. The ulcera- 



218 A TREATISE ON PELLAGRA 

tion of the rectum, according to Marie, 1 has been unduly empha- 
sized. Marie noted twice out of seventy autopsies anemia or hy- 
peremia of the gastric and intestinal mucosa. He also noted 
chronic enteritis with or without cicatrical constriction, thickening 
of Peyer's patches, and cystic degeneration of the submucous 
glands. 

Out of five autopsies Bardin of Petersburg, Virginia, found 
three with tubercular lesions of the intestines. This is a matter 
of importance for the reason that all other sources of diarrhea 
and hemorrhage must be eliminated before we will be aide to draw 
any definite conclusions regarding the role played by pellagra in 
the causation of these symptoms. 

Niles 2 records the findings of E. C. Thrash in two autopsies 
on victims of pellagra in which the conditions were a departure 
from the usual. There was practically no change in the intestinal 
mucosa except a decided thickening in certain parts. This Thicken- 
ing was due to an infiltration of fibrous tissue and the musculature 
had almost entirely disappeared. The changes in the mucosa were 
those of chronic inflammation which was characterized by atrophy 
and disappearance of some of the columnar cells, infiltration of 
the connective tissue stroma, and foci of amyloid infiltration in the 
stroma. It could not be said whether or not this rinding was pecu- 
liar to pellagra or was simply a part of a general cachetic condi- 
tion. It was thought that the pathologic changes of the gastro- 
intestinal tract were due to an effort on the part of nature to 
throw off certain poisons which resulted from perverted metabo- 
lism and atrophic changes of all the. cell structures of the body. 

Harris 3 also found atrophy of the muscular coat of the intes- 
tine. Anemia and hyperemia he found to be more frequent in the 
jejunum and he mentions the liability to the formation of ulcers 
in this same situation but still more so in the ilium. Similar 
changes were found in the colon. Isot infrequently he found the 
walls of the intestine thinned, but this lesion must not be con- 

1 Marie, A., " La Pellagra." 

2 Niles, G. M., " Pellagra: An American Problem," 1912. 

3 Harris, H. F., Trans. Nat. Pel. Cong., 1910. 



THE DIGESTIVE DISTURBANCES 219 

sidered constant as was claimed by the Italian Labus in 1846. 
This claim was contradicted by Morelli and also by a commission 
appointed by the Congress of Geneva in 1847 with the result that 
it was concluded that this condition was inconstant and not to be 
counted as characteristic of the disease. 

The most important post mortem work yet done in this country 
on pellagra was that of the Illinois State Board of Health. A 
summary of this work is as follows : i 

" We have records of eighteen autopsies which were usually 
made about twenty-four hours after death. A summary of the 
findings is given in Table 'No. 3 ; almost all the patients were 
senile and one-half of them showed serious concurrent diseases. 
The only organ which presented striking and constant lesions was 
the colon. In two-thirds of the cases well-marked ulcers were 
found, and from the findings in the stools before death and an 
examination of sections in several cases, most of these may be put 
down as amebic ulcerations. The ulcers were widely distributed, 
deep, and undermined, and gave the surface a ' geographical ' or 
1 moth-eaten ' appearance. The wall of the colon was considerably 
thickened and contracted in places. In one case perforation of 
an ulcer occurred giving rise to an acute peritonitis. In this con- 
nection it is significant that J^eusser speaks of old and recent ulcers 
as a finding in pellagra and another author gives perforation as 
an occasional cause of death. In the remaining cases a well-marked 
folliculitis was present and in seA^eral of these the follicles were 
the large pre-ulcerative ones found in amebic colitis. The lower 
end of the ilium also frequently showed folliculitis. 

" The condition of the colon was such as to arrest one's atten- 
tion and an effort was made to find out how long it had prevailed. 
Autopsy records are available for the past two years. In most 
cases the intestines were not examined. In twelve cases they were 
opened, however, and in eight of these particular mention is made 
of definite ulcerations. One case of multiple abscess of the liver 

1 Bulletin of the 111. State Bd. of Health, Oct., 1909. 



220 A TREATISE ON PELLAGRA 

occurred in a case with ulcerations. These facts speak for them- 
selves." 

It was found in this Illinois investigation that the patients in 
general showed as niuch protozoal infection as did soldiers under 
field conditions in the Philippines, while the pellagrous patients 
showed a much larger percentage of infection. The writer aptly 
says : 

" These findings are confusing in endeavoring to estimate the 
status of diarrhea as an essential symptom of pellagra. The few 
cases in which no protozoa were found had practically no intes- 
tinal disorder, while the remaining cases, showing every gradation 
of disturbance, from a mild diarrhea to a marked and typical dysen- 
tery, had protozoal infections which could, in part, explain the 
local symptoms. The possible bearing of the findings of examina- 
tions of feces on the prevalence of pellagra, will be considered 
under a discussion of epidemiology." 

Many students of the pellagra situation in the United States 
have been impressed with the rather remarkable prevalence of 
amebiasis among the victims. Reference has been made in another 
place to the observations of William Allen in North Carolina on 
this condition and his conclusion will be found to be in accord 
with the Illinois results. Until more work is done along the line 
of a differentiation of the disease-producing amebas from the non- 
pathogenic few conclusions can be drawn. 

The time of the appearance of the diarrhea in pellagra is vari- 
able though it is usual for it to occur with the erythema and stoma- 
titis. It is remarkable how often these three symptoms appear at 
practically the same time, and it is often difficult to gather from 
the patient just when it did appear in relation to the time of the 
appearance of the other two symptoms. 

I have observed the most obstinate constipation in pellagra. 
Its occurrence is a rarity and when found (except in otherwise 
typical cases) always throws a damper on the diagnosis. Eoussel 



THE DIGESTIVE DISTURBANCES 221 

found that it was not altogether infrequent, especially in the early 
stages. It often alternates with diarrhea. 

Strombio, the elder, distinguished the dysenteric type of diar- 
rhea which was characterized by frequent muco-sanguinolent stools 
and colicy pain and which was often seen in the early stages ; the 
other type was the ordinary form of diarrhea so well known to 
all who have seen any of the disease, which is characterized by 
frequent watery stools, and which cannot be checked. It is a not- 
able fact that this diarrhea will resist even large doses of opium 
and never ceases under any form of treatment until the disease 
abates. While the dysenteric type is more frequent in the early 
stages, the serous diarrhea belongs to the later stages and is said 
by Marie to be an important factor in producing the characteristic 
cachexia. It has been stated that there is a peculiar odor to the 
stools in pellagra, and certain writers think that in some cases a 
diagnosis may be made from this alone. I have often been forced 
to endure this odor and I think in some instances it may be charac- 
teristic, but it is as unsafe to rely on it as it is to rely on the charac- 
teristic odor of typhoid fever. The course of this diarrhea is very 
protracted, and it is the rule for it to last throughout the whole 
duration of the disease. Soon after its onset the patient loses 
sphincter control and it is a frequent sight to find the emaciated 
victim wearing a diaper in order to protect the bed. 

L. B. McBrayer of Asheville, North Carolina, has drawn my 
attention to the fact that in the mountainous sections the diarrhea 
is not so frequent as in the low lands, nor is it so intractable when 
it does occur. This is another proof of the variability of the disease 
in different sections. 

Some of the European pellagrologers have taught that the diar- 
rhea of pellagra is a neurosis and has no organic basis in the in- 
testinal tract ; that it is often a symptom of some such condition in 
the cord as myelitis. All that is necessary to disprove this is to 
mention the occurrence of fatal intestinal hemorrhage in uncom- 
plicated pellagra. Such a hemorrhage occurred in the experience 
of J. K. Hall in the State Hospital for the Insane at Morganton, 
North Carolina. The source of the hemorrhage, of course, was an 



222 A TREATISE ON PELLAGRA 

extensive ulcer. This occurrence is not at all frequent and must 
be distinguished from the passages of small amounts of blood so 
often seen in the dysenteric form of the disease. 

It has been stated that pellagra is not a very serious disease 
among children. There are exceptions to this, but it frequently 
happens that a child will never see a physician throughout the 
whole course of the disease. Cachexia is never marked in this 
class of patient, and as one would naturally expect the diarrhea is 
very insignificant and never calls for any very active therapeutic 
measures. 

It frequently occurs that incontinence occurs even in the absence 
of diarrhea. I have seen involuntary movements when the con- 
sistency was almost enough to produce definite form. 

There are many things about the diarrhea of pellagra which 
suggest the diarrhea of sprue. The dysenteric symptoms seen in 
the early stages of pellagra gradually give way to the serous diar- 
rhea ; this same thing occurs in sprue. Probably the best means 
of distinguishing the two conditions is in the character of the 
stools. The distinguishing feature of the stools in sprue is the 
yeasty character. The permanence of the looseness of the bowels 
after the subsidence of active symptoms occurs in both diseases. 
Long after a case of pellagra is pronounced cured there will remain 
that tendency for the slightest irritant to produce diarrhea. It 
would almost seem in some cases that a diarrhea habit had been 
developed. 

The liver is subject to certain changes in pellagra. The organ 
may be slightly enlarged and friable or it may be decreased in 
size. Brown atrophy has occurred. Verga reported the occur- 
rence of cirrhosis. By actual weight the liver may be found to be 
diminished and according to some writers this diminution may 
reach one-half. Fatty infiltration and sometimes congestion or 
granulo-fatty degeneration are reported by Marie. Chiarugi in 
twenty-nine autopsies found nine fatty livers. In five of Harris' 
autopsies the post mortem weight was only once as much as 
1010 grams. He found microscopically the cells of the peripheral 
portion of the lobules frequently quite fatty, though this change 



THE DIGESTIVE DISTURBANCES 223 

could not be considered distinctive of pellagra. He found that in 
some cases the central vein of the lobule was dilated. In the Illi- 
nois pellagra report in their eighteen autopsies the liver was fatty 
in five, in two it was fibrous, in one there were gallstones and 
adhesions, in one empyema of the gall bladder, in one passive con- 
gestion, in one slight cirrhosis, in six it was normal. I have never 
seen in pellagra symptoms referable to the liver though such a 
coincidence may occur. So far as I have been able to find in the 
literature there has never been an instance where the liver pro- 
duced any definite symptoms. 

The pancreas is not affected by pellagra as far as is known at 
the present time, though Harris refers to a slight atrophy which 
could be probably accounted for by some other disease process. 



CHAPTER VI 

NERVOUS AND MENTAL CHANGES IN PELLAGRA 

Many of the European pellagrologers have always contended 
that pellagra should be classified in the group of psycho-neuroses. 
In a previous chapter an effort has been made to show that it is 
not a skin disease and has no more right to such a classifica- 
tion than has syphilis. Contrary to the opinion of Strombio, 
the elder, there is certainly no justification in the classifica- 
tion of it as a gastrointestinal disease. As in Europe the final 
result of pellagra is invariably a psycho-neurosis, we can readily 
appreciate the point of view that places the disease in this cate- 
gory. The experience with the disease in the United States 
demonstrates the insufficiency even of this classification. Prob- 
ably there has been a greater death rate from pellagra in 
individuals manifesting no nervous symptoms than otherwise. 
Such has certainly been my experience and has been borne out 
by my autopsies. In this chapter I will have little to say about 
my personal experience with the pathologic changes produced by 
pellagra, for the reason that my results in the large majority of 
instances have been negative. The reason for this can be readily 
appreciated when one remembers that these changes are the result 
of repeated attacks on the nervous system. It is only rarely that 
one attack is sufficient to produce demonstrable effects on the 
nervous tissue. An exception to this rule will be recorded later. 
Again, it will be stated later that definite psychical distur- 
bances may occur early in the course of the disease without any 
changes in the brain tissue which could be detected with the 
most modern methods. It is true that the probable outcome of 
the ordinary types of pellagra will be insanity, and it is this 
phase w T hich makes of the disease a great sociological problem. 



NERVOUS AND MENTAL CHANGES IN PELLAGRA 225 

Up until this time pellagra in this country, as mentioned above, 
has been either acute or sub-acute in many instances and the vic- 
tims have succumbed before there was time for the occurrence 
of any organic lesion of the nervous system. The disease is now 
assuming rapidly the form seen in Italy, and in another year it 
seems probable that all differences between the disease on the 
two continents will have disappeared and there will be a repe- 
tition of that peculiar property of diseases so well illustrated in 
the outbreak of measles in the South Sea Islands. It will be 
recalled that when this disease first appeared in that country 
the death rate was over ninety per cent, but now the disease 
has assumed normal proportions. Just such a thing seems to be 
occurring in the pellagra situation in the southern states. It will 
only be a question of time before the insane institutions of the 
South and possibly of other sections will be shown to be utterly 
inadequate on account of the great increase in insanity which 
will be brought about by pellagra. Already in many states there 
is the great evil of over-crowding. One of the pioneers in the 
movement for better facilities for the insane is South Carolina, 
headed by J. W. Babcock, an authority not only on the insti- 
tutional care of these poor unfortunates, but also on the pellagrous 
psychoses. This new institution of South Carolina will be built 
on modern lines throughout, but in addition to the usual meaning 
of this expression, the pellagrous insane will be provided with 
accommodations suitable to their particular needs. 

There seems no more reason for the classification of pellagra 
as a nervous disease than for the same classification of syphilis, 
which also has manifestations in both the skin and nervous system. 
There are many points of similarity between pellagra and lues, 
which will be noted later. Until the question of the etiology of 
pellagra is definitely settled it must remain in an unclassified 
state. If it were necessary at this time to make an arbitrary 
classification I would place it in that group of diseases due to 
an animal parasitic cause, such as syphilis, trypanosomiasis, kala- 
azar, Rocky Mountain fever, and malaria. The basis for this 
classification would not be a leaning towards the teaching of 



226 A TREATISE ON PELLAGRA 

Sambon, but would be due to a belief that a disease of unknown 
cause had best be classified on a pathologic basis. 

Throughout the study of the nervous system of pellagra the 
student is constantly impressed with the similarity to syphilis. 
The changes in the tissue at autopsy are very much like the changes 
of syphilis. In addition to this the seasonal variations, the pro- 
gressive character of the nervous changes, and the resulting 
psychical disturbances, as well as many other symptoms which could 
be mentioned, tend to emphasize this similarity. Tuczek goes 
so far as to record a condition of dementia paralytica produced 
by pellagra, though the usually accepted teaching at this time 
is that syphilis alone causes this mental state. 

A comparison from a nervous standpoint of pellagra with ergot- 
ism is a matter of considerable interest, especially in the light 
of the fact that the two diseases have always been linked together 
in the group of diseases due to grain intoxication; in addition 
to this there are many points of anatomical similarity which 
would suggest a connection, though the resemblance is not so 
marked between pellagra and ergotism as between pellagra and 
syphilis. That brilliant pellagrologer, F. Tuczek, whose work on 
the nervous pathology of pellagra is the be^t on the subject, is 
outspoken in his declaration of a marked similarity between 
pellagra and ergotism, based on the following facts which can but 
impress one with their reasonableness : In both diseases j:here is 
an undoubted intoxication process and, preceding the nervous and 
skin manifestations in both, there is almost invariably a dis- 
turbance of the whole gastrointestinal tract. Following a pro- 
longed chronic course in both diseases, cachexia closes the scene. 
The character of the psychosis, especially that stuporous form of 
melancholia, is alike in both conditions. In both there occur 
disturbances of the sensory, the motor, and the vasomotor systems. 
In ergotism there is a marked tendency for the involvement of 
the spinal cord to affect the posterior columns, while in pellagra 
it is the lateral columns which are more usually the seat of the 
degenerative process. In my own series there was a peculiar 
frequency of involvement of the posterior columns, and some of 



NERVOUS AND MENTAL CHANGES IN PELLAGRA 227 

my best pathologic specimens illustrate this occurrence. In ergot- 
ism the posterior roots are degenerated and also the column of 
Burdach in the cord. The column of Goll is said not to be 
primarily affected but may be involved secondarily in advanced 
cases (Adami). 1 In addition to this, the anterior root zone, the 
median portion of the middle zone, and Lissauer's tract escape 
in ergotism. The posterior roots are not involved in pellagra, and 
for this reason Marie regards it as an endogenous disease of the 
spinal cord. This failure of the involvement of the posterior roots 
when the posterior columns are the seat of a definite degenerative 
process is very characteristic of pellagra and is shown in the 
microphotographs. 

It will be noted in ergot poisoning that the initial symptoms 
distinguish it as an acute gastrointestinal intoxication process 
having its point of attack in the digestive tract. Later on its 
chief manifestation is as a vaso-constrictor, and this seems to 
be the predominant action of the poison throughout. There is 
a rise of blood pressure, and the vessels primarily or secondarily 
undergo a hyaline degeneration which is shown chiefly in the 
tunica intima. The local manifestations of gangrene are more 
or less the result of this constrictor process. In pellagra it will 
be noted that the blood pressure is lowered throughout and there 
can be no connection between the erythema and any circulatory 
disturbance as there is between the gangrene of ergot and the 
vaso-constriction. 

Medical students are taught there are two nervous diseases 
which do not follow any of the rules of classification; that in 
these two conditions symptoms occur which are found in many 
other diseases, but there may be a great combination of such symp- 
toms, making the disease appear as a hybrid, but usually lacking 
the pathognomonic symptom of any one. These two diseases 
are syphilis and hysteria. The latter will explain itself in time, 
as it is a functional disturbance, but the former offers more 
difficulties. A third disease which offers the same difficulties in 
pellagrous localities is pellagra. When the patient is seen for the 

1 Adami, G. J., "Pathology," 1911. 



228 A TREATISE ON PELLAGRA 

first time between the attacks of erythema and when the pre- 
existing erythema had been very slight, often not impressing the 
patient or the family as a matter of any note, there is a con- 
dition to be reckoned with which may often be classified either 
as hysteria or syphilis. It is true that the Wasserman and Xoguchi 
tests form valuable adjuncts in avoiding an error, but again a 
difficulty arises in the fact that some observers find a positive 
reaction in the Wasserman test in pellagra, though it is counted 
fainter than in syphilis. It is a daily problem with me and my 
colleagues to differentiate between myelitis of specific origin and 
similar pathologic conditions produced by pellagra. Recently, 
a patient under my care in the James Walker Memorial Hospital 
in Wilmington, North Carolina, who was familiar with the symp- 
tomatology of pellagra because a member of his family had been 
a victim of the disease, gave us a good history of the malady in 
order to throw us off the scent of the real disorder. He claimed 
to have had an erythema of the face and hands and really pre- 
sented some spurious traces of a skin lesion. His reflexes were 
all abolished, tactile and temperature sense much perverted, and 
he had incontinence of the bowel and bladder with trophic dis- 
turbances. Very tearfully he denied syphilis, and in the light 
of his history and the presence of a stomatitis and intestinal dis- 
turbances a tentative diagnosis of pellagra was made, pending a 
Xoguchi test. The result of this examination was a very positive 
reaction. 

The pathologic changes which occur in the nervous system in 
pellagra are of great interest and importance. Tuczek spoke of 
these changes as heterogeneous. The pigmentation which occurs 
especially in the ganglion cells is also found normally in old age. 
Hyperemia, anemia, and edema of the central nervous system 
and its coverings cannot be counted as distinctive of pellagra. 
The same thing occurs in a number of other conditions, as chronic 
spinal and cerebral pachymeningitis and leptomeningitis and 
spinal arachinitis. The obliteration of the central canal of the 
cord occurs in many chronic affections of the central nervous 
system. The findings in the brain in pellagra are usually negative 



NERVOUS AND MENTAL CHANGES IN PELLAGRA 229 

apart from the occasional occurrence of fatty degeneration or 
calcification of the intima of the small blood vessels and pig- 
mentation of the adventitial coats. In long-continued psychoses 
resulting in high degrees of imbecility, atrophy of the cerebrum, 
chiefly of the cortical substance, is said to occur. The essential 
changes are to be found in the spinal cord. Tuczek mentions the 
abnormally rich pigmentation of the nerve cells in the cord as 
well as in the spinal and sympathetic ganglia, which is frequently 









M 


&\ I ■;;<■■ 


<:,. 


;. 




Hk^lr 


i% »Fji 




1; 


^^jB 




•"". .../- 


m 


}fe 


' 



Fig. 29 (a). — Upper Dorsal Cord of 17-year-old Girl. (Case of Dr. R. H. 
Bellamy. Preparation of Dr. H. A. Cotton.) 

called pigment atrophy, though such an interpretation of the 
condition is an error. Bouchard compares the findings in the 
cord to the pathologic anatomy of tabes dorsalis. 

The location of the areas of degeneration in the spinal cord are 
clearly indicated by the type of the nervous symptoms. As above 
mentioned, the posterior columns are sometimes involved, though 
probably not so frequently as the lateral tracts. When the posterior 
columns are affected the median portions are more often degen- 
erated, but the posterior root zones are never affected. The brunt of 
the process falls on the crossed pyramidal tracts. The direct cere- 



230 A TREATISE ON PELLAGRA 

bellar tracts are not involved. The cells of the anterior horns are 
usually decidedly pigmented. In the late stages muscular atrophy 
of a general character occurs, but it selects no particular portion 
of the body. The lesions of the posterior columns occur chiefly 
in the cervical and uj)per dorsal regions. The microphotographs 



y*^-^ga 


k 


'sfl^H 






4 






r < H i 




c 


4 sW 







Fig. 29 (6). — Mid-dorsal Cord of 17-year-old Girl. (Case of Dr. R. H. 
Bellamy. Preparation of Dr. H. A. Cotton.) 

show a cord with the posterior columns affected. The affection 
was chiefly in the dorsal segment, the cervical and lumbar seg- 
ments being only slightly involved. The patient was a negro 
girl of seventeen years whom I saw through the courtesy of my 
colleague, R. H. Bellamy. It is a remarkable case, for the reason 
that the patient died in the first attack, and in our experience it 
has been the rule that definite organic changes do not occur until 
after the existence of the disease for at least three years. In this 



NERVOUS AND MENTAL CHANGES IN PELLAGRA 231 

case the disease appeared early in May, 1909. The first symptom 
was stomatitis, which was soon followed by diarrhea and later by 
the characteristic erythema which the patient mistook for sun- 
burn. The erythema was confined to the dorsal surfaces of the 
hands and forearms, the under surface of each elbow, and small 




Fig. 29 (c). — Microphotograph of the Lower Dorsal Cord of 17-year-old 
Negro Girl. (Case of Dr. R. H. Bellamy. Preparation of Dr. H. A. Cotton.) 



areas beneath each knee. In all instances the symmetry was 
perfect. She was first seen on June 12, 1909. At that time 
she had been suffering for a week with severe pains in the lumbar 
region, which radiated into each hip posteriorly. During the 
preceding twenty-four hours she had lost the use of the lower 
limbs. On July 7 the systolic blood pressure was 110. She 
complained of burning and tingling pain from the crest of the 
ilia downward, involving the upper one-fifth of the thighs. Pre- 



232 A TREATISE ON PELLAGRA 

viously in this area there had been a loss of tactile sense, but 
at this time there was a return of this sense. She was also able 
to move the thighs, but it was done by the psoas and quadratus 
muscles and the movement was very slight. This had not been 




Fig. 29 (d). — Microphotograph of the Dorsal Cord of 17-year-old Girl 
(Negro). (Case of Dr. R. H. Bellamy. Preparation of Dr. H. A. Cotton.) 



possible at the previous examinations, as these muscles too had 
shared in the general process of paresis. On July 12 it was 
noted in Doctor Bellamy's record that the areas of anesthesia were 
about the same and there was no change in the motor condition ; 
diarrhea was more aggravated and emaciation was extreme. In 
spite of good attention bed sores developed. On July 17 tactile 



NERVOUS AND MENTAL CHANGES IN PELLAGRA 233 

sense was found to be improving. The areas in which sensation 
had returned extended to the junction of the middle and upper 
thirds of the thigh. In these areas of returning sensation the 
patient complained of burning pain. She was nauseated and 
very irritable and the volume of the pulse was poor. There was 
a decided disturbance of temperature sense and total motor paraly- 
sis, together with inability to void the urine. She was catheterized 
without experiencing any sensation of the operation. The tem- 
perature was 101° F. and the pulse 100. On July 18 there was 
little change except that the power to appreciate a full bladder 
and ability to void the urine had returned. The temperature at 
this time was 101.4° F. and pulse 110. Her clouded mentality 
was improving. The stomatitis was less, but the diarrhea per- 
sistent. On July 23 the erythema was rapidly subsiding and 
there was an improvement in the mouth and intestinal symptoms. 
The nervous condition was practically unchanged. The motor 
paralysis from the crests of the ilia downward was complete. 
July 28. ~No change in the nervous system. The feet were quite 
edematous. Temperature was 100° F. and pulse 96, being of 
good volume. The patient seemed to be stuporous, and it was 
necessary to arouse her in order to question her; throughout the 
examination she remained in this state. The heart and lungs 
were negative and the abdomen also, except for a tender area 
in the epigastrium. The pupils were equal and responded both 
to light and accommodation. The blood showed a secondary anemia 
of moderate degree and no leucocytosis. The urine was negative. 
There was total motor and sensory paralysis of the lower ex- 
tremities and an absence of all reflexes. On August 7 she was 
vomiting, her feet were very edematous, and the pulse was of 
poor volume. She was able to move the toes very slightly. The 
reflexes were absent. On August 14 the anesthesia had disap- 
peared from the toes to the knees and the sensation of burning 
and tingling had returned. She was able to move her toes fairly 
well. Enormous bed sores had developed. The temperature was 
100° F. and the pulse 120. 

A few days after this last observation the patient died during 



234 



A TREATISE ON PELLAGRA 



a spell of very hot weather. Her home was in an isolated place 
many miles from us, and the autopsy was unavoidably delayed, 
and when done could be only partial owing to the fact that the 
negroes were threatening us and we were forced to work very 
hurriedly. Consequently we were very glad to escape with our 
lives and the spinal cord in a solution of formalin. II. A. Cotton 
of the State Hospital for the Insane of Xew Jersey at Trenton 
kindly prepared the material. On holding these preparations up 
to the light one would suspect at once that the lesion was that 
of locomotor ataxia, but, as mentioned in pellagra, the posterior 
roots are not involved in the degenerative process as in the former 
disease. 

Tuczek 1 made exhaustive studies of eighl cases of pellagra, 
and his findings are of great interest and importance. Seven of 
these eight cases show r ed degeneration of the posterior columns 
of the cord. In one it was limited to Goll's column and a medial 
strip of Burdach's. In five cases it extended throughout the 
whole length of the cord. In one case the involvement was con- 
fined to the cervical segment. In four the dorsal region was the 
chief seat of degeneration. In five cases the crossed pyramidal 
tract was affected. In the first the affected areas extended from 
the upper cervical to the upper dorsal with degeneration of the 
cells in the anterior and posterior horns in the middle and lower 
cervical regions; in the upper dorsal region there was found 
atrophy of the cells in the anterior horns and the column of 
Clark, as well as atrophy of the anterior root fibers. In the 
second the degeneration of the crossed pyramidal tracts was 
more intense in the dorsal region, but extended as high upward 
as the middle cervical and as low as the upper dorsal regions. 
In the third case the lesion extended throughout the cord, but 
was more marked in the dorsal portion. In the fourth case 
the lesion was confined to the dorsal portion. In the fifth the 
degeneration was massive and limited to the middle cervical 
region. 

In one of Tuczek's cases in the middle cervical region the 



1 Tuczek, F., " Klin. u. anatom. Studien ueber die Pellagra." 1893. 



NERVOUS AND MENTAL CHANGES IN PELLAGRA 235 

left anterior horn was constricted to the point of complete sepa- 
ration ; the posterior columns formed an angle with each other ; 
the anterior fissure was displaced and removed through the white 
commissure. The central canal of the cord is often dislocated 
and in one instance it was doubled. Clark's column may be 
displaced, and in one instance in the upper portion of the cord 
it was drawn to the right and in the lower portion to the left, 
but the elements of the columns were normal. The central canal 
is liable to be obliterated at any level. Corpora amylacea were 
abundant in the region of the central canal and entered the 
posterior roots as well as the septum posticum in the posterior horns 
and in Goll's column. The posterior columns may be the situ- 
ation of a bilateral symmetrical degeneration, which is indicated 
by an atrophy of nerve fibers and an increase in the size of the 
interstices. The ganglion cells are found to be rich in pigment 
and in the affected areas there is a degeneration or absence of 
nuclei and processes. In some instances there occurred small 
masses of pigment drawn together, while in others the nuclei 
were scarcely visible. Occasionally vacuolation was found. The 
chief seat of the degenerated atrophic ganglion cells was in the 
periphery of the cortex. The fine net-like fibers were found to 
be richly developed in -the cortical region of the anterior horns. 
In one instance there was found in the center of the anterior horn 
in the lower cervical region a small polio-myelitic focus. In the 
lumbar cord throughout the whole medullary sheath were found 
large spindle cells, which may occur in all tracts. The pia mater 
showed no alterations and nothing abnormal was noted, as a rule, 
in the blood vessels. In the degenerated postero-lateral tracts 
there was noted in one case a slight increase in the nuclei. The 
anterior roots of the spinal nerves may be atrophied. Glia cells 
in the anterior horns are sometimes rich in pigment. The cover- 
ings of the cord, as previously mentioned, are invariably normal. 
Kornchen cells are found exclusively in the postero-lateral tracts. 
The diseased tracts present a uniform sclerosis with atrophy of 
nerve fibers, separation of the interstices, and striking nuclear 
increase. Changes in the central canal of the cord often suggest 



236 



A TREATISE ON PELLAGRA 



syringomyelia, and it is further difficult in many cases to explain 
the trophic and anesthetic symptoms by the skin changes. 

Mariani's finding of constant arterio-sclerosis is not borne out 
generally by other observers. Extension of the perivascular spaces 
may occur in the cord as well as in the cerebral cortex. 

The glia tissue of the commissure is often much increased, 
and this fact is confirmed by Golgi, Tuczek, Lukacs, and Fabinyi. 
The last two of these observers found extreme extension of the 
perivascular space of all three of the central arteries and thought 
that it was directly related to the occurrence of the pellagrous 
process. These same observers found that disintegration of the 
sheath of the spinal cord was nowhere complete, but was most 
decided in the region of the cervical vertebrae. They thought 
that in all probability this was related to the fact that beginning 
at this point and continuing downwards many cells of the pos- 
terior cornua were degenerated. This was confirmatory of the 
view of Babes, who thought that the disintegration of the sheath 
was of endogenous origin. The gray degeneration of the column 
of Goll was found to be especially frequent in pellagra. Tuczek 
and Marie stated that this process, combined with degeneration 
of the lateral tracts, presented a characteristic of a systemic disease. 
Lukacs and Fabinyi, 1 however, were inclined to the view of 
Babes, which attributed the degeneration of the spinal cord to 
a selective process caused by the degeneration of the ganglia, or, 
possibly also, to the endogenous result of the disappearance of the 
cells of the posterior cornua. The fact that many fibers remain 
uninjured favors this view. These observers differentiate the 
disease of the cord in pellagra from tabes dorsalis by the fact 
that the degeneration in the former is confined to the cervical 
cord (Belmondo) and by the lack of any involvement of Lis- 
sauer's tract. They also found the cells of Clark's column degen- 
erated to a marked degree. The above-mentioned view of Bel- 
mondo regarding the limitation of the degenerative process to the 
cervical portion of the cord is not invariable. It may be said, 

1 Lukacs and Fabinyi, " Allgemeine Zeitschrift fuer Psyckiatrie." Vol. 
LXV, Part 4. Aug. 29,' 1908. 



NERVOUS AND MENTAL CHANGES IN PELLAGRA 237 

however, that locomotor ataxia does cause more pathologic changes 
in the dorsal and lumbar cord than does pellagra. 

The sensory cells of the posterior cornua show less changes than 
the badly diseased cells of the anterior cornua, which are affected 
in the cervical region. The column of Clark is especially affected 
and the cells show a homogeneous swelling with nucleolysis and 
chromatolysis and the remains of the chromatin form a wreath 
at the circumference. Katonsky noted a granular condition of 
the glia cells. In cachectic cases melanosis is frequent, and this 
resulted in the conclusion of Tinotti and Tedeshi that the con- 
dition is allied to Addison's disease. Babes found the lesions 
of the cord closely resembling those of tabes, such as degeneration 
of the posterior roots of the spinal nerves and the posterior col- 
umns. It was also found that those lesions were more frequent 
in the cervical segment. In the chronic form of the disease run- 
ning a very close course the anatomico-pathological alterations 
are very similar to those of progressive paralysis and tabes dor- 
salis. In 1899 Babes and Sion made a valuable contribution 
to the study of the neuro-pathology of pellagra. They found 
in the nerve cells, especially the large chromophilic cells of the 
cortex, signs of unquestionable degenerative changes. The tigroid 
bodies lost the power of staining with the basic dyes and the cells 
became swollen and vacuolated. The nuclei were pushed aside 
and lost the power of taking the basic stains and presented swollen 
nucleoli ; the pigment in these cells was also dislocated, and instead 
of being around the nucleus lay scattered throughout the cell 
body. The processes of the cell appeared to be broken off and 
seemed swollen. The perivascular lymph spaces were dilated and 
the walls of these cavities were frequently lined with yellow pig- 
ment. In the brain tissue small collections of lymphoid cells 
were frequently encountered and the neuroglia cells in the vicinity 
of the blood vessels were swollen. These alterations have been 
in the main confirmed by Marinesco, Rossi, Richette and Grimaldi, 
and Harris 1 in this country. The last-mentioned observer adds 
that the small vessels of the brain seemed unusually filled with 

1 Harris, H. F., Trans. Nat. Pel. Cong., 1910. 



238 



A TREATISE ON PELLAGRA 



blood and the perivascular lymph spaces quite uniformly dilated. 
There were no collections of lymphoid cells anywhere in the tis- 
sues. The nerve cells showing degenerative changes usually meas- 
ured less than the normal cells and always contained a greater or 
less amount of acidophilic protoplasm. He found that the cells 
in different portions of the brain suffered in varying degree. 
Perhon and Papinian, according to Harris, have demonstrated, 
as would be expected, that the neuro-fibrils of the cells show de- 
generative changes. Alterations similar to those found in the 
cerebrum have been observed by Harris in the nerve cells of 
Purkinje. The cell protoplasm was found to lose its affinity for 
basic stains, and the nuclei underwent a similar change. Harris 
states that the nerve cells showed every stage of degeneration from 
slight loss of chromophilic substance to practical destruction of 
the cell body. He found the changes in the cord to be confined 
chiefly to the lower cervical and dorsal segments. 

It is interesting at this point to note the distinction drawn by 
Lombroso between pellagra and tabes dorsalis. He said that in 
most instances typical cases suggested locomotor ataxia in its 
incipiency, with the differences that in pellagra few changes were 
found below the dorsal region, while in tabes the lumbar region 
is chiefly affected, though the cervical segment may be most in- 
volved. Both diseases, he said, show degenerative changes in 
different portions of the spinal cord, while tabes attacked the 
posterior columns especially and pellagra the lateral or both 
posterior and lateral. Both diseases presented the picture of 
a combination sclerosis. Marie thought that the sclerosis of 
pellagra resembled more closely that of general paresis than 
tabes. It was further noted that edema of the central nervous 
system and a chronic leptomeningitis is common to general paresis 
and pellagra, Rohrer s * view of the pathology of pellagra is that 
it should be classified with the infective granulomata. He says 
that the small tumor-like nodules or granulomata are seen to be 
composed of a necrotic center surrounded by spindle-shaped cells 
and small round cells, very similar to tubercles or gum.mata with- 

1 Rohrer, C. W. G., Trans. Nat. Pellagra Cong., 1909, p. 145 et seq. 



NERVOUS AND MENTAL CHANGES IN PELLAGRA 239 

out giant cells. These granulomata he found most abundent in the 
walls of the superficial blood vessels of the lungs, but especially 
the upper lobe of the right lung. After the lung, in order of 
abundance, were the superficial blood vessels of the brain, which, 
he claimed, furnished a pathologic basis for the distressing 
mental symptoms which were apparent in the last stage of the 
disease. 

Randolph and Green * mentioned the finding of a glistening 
dura, a thickened pia, and small hard plaques in the arachnoid, 
which was also noted by Lombroso. 

Marie 2 found opacity of the pia mater and thickening of the 
pia and arachnoid, which in some instances was circumscribed but 
more often diffuse. This condition occurred with a purulent 
exudate or with hemorrhagic extravasation under the arachnoid. 
In some instances there was found extensive or partial edema of 
the brain, to which was often added edematous softening around 
the pillars of the fornix or at the foot of the hippocampus. Five 
times in one hundred and thirteen autopsies was found hardening 
of the cerebellum, while in eight cases of the same series it was 
soft and edematous. In eleven instances there was atrophy of 
the brain, especially in the cortical substance. In eighteen out of 
twenty-eight cases examined the weight of the brain was dimin- 
ished, while in seven it was increased above normal. In five 
instances hyperemia of the brain was noted, twice of the corpus 
striatum, in one more marked on the right than the left. In four 
cases there was anemia of the brain. Marie 2 recorded the fol- 
lowing findings from the literature : 

Nardi, Fanzago, and Strombio reported injection of the mem- 
branes with thickening of the arachnoid and congestion of the 
sinuses. In most of his autopsies Liberali found inflammatory 
changes in the arachnoid. In twenty-one out of forty-one cases 
Verga found adhesions of the dura mater to the superior cranial 
bones ; twice thickening of the dura mater ; three times opacities 

1 Randolph and Green, Ibid. 

- Marie, A., " La Pellagra," and authorized translation with notes by Lavin- 
der and Babcock. 



240 A TREATISE ON PELLAGRA 

of the arachnoid; and in one case only was there adhesions 
of the pia mater. In sixteen autopsies Rizzi found the pia in- 
volved in everv instance. Morelli found extravasations of blood 
beneath the meninges very frequently. Verga in eight cases found 
hydrops of the ventricles and four times softening of the cerebral 
substance. Microscopic examination showed in eleven instances 
a fatty or pigmentary degeneration ; in four cases the two were 
combined in the walls of the cerebral capillaries; three cases 
with calcareous degeneration; one instance of sclerotic changes 
in the brain; one case of dilatation of the capillaries of the 
brain. Out of twelve examinations of the sympathetic ganglia, 
decided pigmentation of the ganglion cells was found in eight 
instances. 

Leonardo Bianchi * said : 

". . . I must make special mention of the alterations of the 
abdominal sympathetic system (Babes and Fox), and the paren- 
chymatous neuritis found by Dejerine. In the brain Ave find 
thickening, turbidity, and often adhesions of the meninges, atrophy 
and induration of the cerebral substance, increase of the suit- 
arachnoid fluid, profound alteration of the cerebral cells, and 
increase of the neuroglia. In the acute cases the usual cell alter- 
ations are those found in other acute forms of psychosis. In the 
spinal medulla lesions are found in the various bundles (Tonnini), 
just as in progressive paralysis. In one case the pyramidal bun- 
dles are most affected, in another the sensory bundles, in a third 
the central substance." 

Tuczek's findings in the cells of the central nervous system 
were essentially the changes of parenchymatous nature. The 
chromatolysis was advanced even to the point of destruction of 
the chromatophilic substance, together with swelling, vacuoliza- 
tion, and nucleo-atrophy. These changes were chiefly of the nerve 
cells of the cerebrum and especially of the paracentral gyrus, 

1 Bianchi. Leonardo: "Pellagrous Insanity" in '"'Textbook of Psychiatry," 
translated bv J. H. Macdonald. i<)06. 



NERVOUS AND MENTAL CHANGES IN PELLAGRA 241 

of the medulla oblongata, and of the cord. In one of his cases 
with the symptom complex of progressive paralysis he found a 
breaking up of the medullated fibers of the cerebrum just as 
typically occurs in dementia paralytica. In the discussion of 
a paper read by me 1 before the College of Physicians of Phila- 
delphia recently, H. A. Cotton mentioned a class of cases de- 
scribed by Adolph Meyer under the name. " central neuritis " and 
thought that the mental symptoms presented by some of my cases 
strongly suggested this condition. This idea is strongly borne 
out by the statement of Siler who thinks that pellagra occurs in 
practically all the insane institutions in the United States. Cot- 
ton mentioned the occurrence in these cases of stupor or anxious 
delirium together with rigidity, peculiar muscular spasms or 
jactitations, and obstinate diarrhea. All of the cases observed 
by him ended fatally. He said that the etiology of central neuritis 
was obscure, but it was undoubtedly due to an intoxication. The 
histo-pathology has been definitely described and can be easily 
diagnosed by a competent neuro-pathologist. While the two 
diseases cannot be counted altogether similar, still they probably 
arose from the same pathological process. Soon after this I sent 
a brain and cord from a rather atypical case of pellagra to Doctor 
Cotton for a further investigation of this interesting point. He 
wrote me in reply: 

" My suspicions regarding the similarity of this process with that 
of central neuritis is well borne out in this case. The large motor 
cells and a great many cells, in other regions show ' axonal re- 
action ' to a very marked degree. 

" The condition has been somewhat described by Marinesco 
and other Italian observers as ' chromatolysis,' but none of them 
have recognized that it is an ' axonal reaction.' In other words, 
it is a parenchymatous degeneration of the central nervous system." 

A marked similarity will be found in this description and that of 
Tuczek and others of pellagra. The matter certainly deserves 

. 1 Wood, E. J., " Appearance of Pellagra in the United States." Trans. Col- 
lege of Physicians of Phila. 1909. 



242 A TREATISE ON PELLAGRA 

further investigation. If a definite pathologic basis can be found, 
many of the cases of so-called " pellagra-sine-pellagra " can be 
cleared up and a clinical study of this condition, if such a con- 
dition exists, can be made and it can thereby be placed on a more 
satisfactory footing. It is not at all improbable that many of the 
cases in our state institutions with the diagnosis of dementia 
paralytica really belong to the group of pellagra psychoses. Such 
a possibility has been mentioned on a previous page, and I can 
state of my own knowledge that such an error is by no means 
rare in some institutions where the cases are definitely and care- 
fully classified, and such a thing is not at all surprising when 
such a distinguished neuro-pathologist as well as pellagrologer, 
as Tuczek should make the statement that he found a definite 
condition of dementia paralytica in one of his cases of uncom- 
plicated pellagra. 

Tuczek emphasizes the fact set forth earlier in this chapter 
that the nervous disturbances in pellagra remain for a long time 
on the border line between functional affections and fixed patho- 
logic processes. This is manifested by the occurrence of im- 
provement of symptoms on the one hand and by fixedness on the 
other. It also is manifested by diffuseness on the one hand and 
localizing properties on the other. He says that a tendency to 
progressiveness is a characteristic sign of pellagra. Xumerous 
cases from my records will be introduced to show this point. It 
will be seen that in many instances from the character of the 
symptoms one would have good ground to look for definite organic 
changes in the nervous system, and yet these signs will be wanting 
at autopsy in spite of the employment of the most improved 
methods of pathologic technique. One case in particular, studied 
clinically by me and microscopically by Doctor Cotton, will now be 
recorded. This case was described in the beginning (December 
7, 190T) under the title " A Mixed Infection with Tertian and 
Quartan Malaria Occurring in a Patient with Symmetrical Gan- 
grene." 1 It was not recognized at that time as a case of pellagra 
and, as previously stated, I was indebted to Searcy and others 

1 Wood, E. J., Jour. Am. Med. Assoc, XLIX. p. 1S91. 1907. 



NERVOUS AND MENTAL CHANGES IN PELLAGRA 243 

in Alabama for setting me straight in supplying the proper diag- 
nosis. While at work in the laboratory of Alois Alzheimer in 
Kraeplein's clinic in Munich, Doctor Cotton became interested in 
my pathologic material which I had with me and since that time 
has given me the benefit of his skill as a neuro-pathologist. 

The patient was a man, aged 46 ; his occupation was that of 
a grocer. There was nothing of note in his previous medical his- 
tory except an absence of syphilis and malaria. He was a re- 
markably strong, robust man. The beginning of his sickness 
occurred without any prodrome, with high fever which developed 
during the night and was followed by a profuse sweat. One week 
later his wife noticed that he was acting peculiarly. Among the 
strange things which she noticed was that he would ring his own 
door bell instead of using his night latch. He seemed to be 
dazed and was unable to attend to his business, making many 
absurd mistakes. There were no outbursts and no other mental 
changes noticed except this dazed condition and a general apathy. 

For six months his condition remained unchanged. At this 
time his mental disturbance became much exaggerated and there 
was added to the previous symptoms utter indifference to every- 
thing. His bowels and bladder would be emptied in bed and 
the patient was apparently oblivious to his filthy condition. There 
was marked muscular weakness. Speech was slow and somewhat 
hesitating. There was some tremor present. The reflexes were 
rather sluggish. Pupils reacted to light and accommodation. The 
tests showed an absence of temperature sense and a great impair- 
ment of tactile sense. For the greater portion of the time this 
patient remained quietly in bed. On the back of each hand was 
an area of exfoliating skin. The two areas were symmetrical 
in position, shape, and size. The erythematous process was practi- 
cally over at this time. The patient told me that during the pre- 
ceding month he had had several chills, for which he was given 
quinine. This was nine months after the beginning of the 
affection. About three months later, on October 27, 1905, he 
was admitted to the James Walker Memorial Hospital in Wil- 
mington, North Carolina. At this time the posterior surfaces 



244 A TREATISE ON PELLAGRA 

of both bauds were affected with a dry exfoliative Lesion extend- 
ing from the tips of the fingers to two inches above the wrist joints 
and the lines of demarcation were perfectly symmetrical in posi- 
tion and direction (Fig. 23). Tlie ringer tips were considerably 
atrophic, corresponding in this regard to the classical description 
of Raynaud's disease. The lesions wire painless. On the ex- 
ternal surface of the right leg. involving the lower third of the 
lower leg and the external surface of the foot, was a large moist 
ulcerative area penetrating to the muscle (Fig. 22). On the 
left leg was a much smaller area of the dry exfoliative variety. 
This leg manifested at times the appearance of a local syncope, 
becoming cold and apparently bloodless, and again it would be- 
come cyanotic. As the chart shows (Chart II) the temperature 
at this time and for a period certainly of three weeks, never rose 
above 99.0° F. There was an absence of chills. The heart, 
lungs, kidneys, and liver were negative on examination. There 
was a simple secondary anemia and no leukocytosis. There was 
nothing suggestive of malaria, and yet during these three weeks 
the blood was loaded with tertian parasites in all stages of develop- 
ment. According to Craig, latent malaria is often characterized 
by organisms in all stages. Latent malaria in the southern states 
is practically unknown. In the routine examination of the blood 
for malarial parasites this is the only case found out of several 
hundred examinations. In spite of the presence of the parasites 
in the blood the temperature remained practically normal and the 
lesions progressed favorably. 

On Xovember 29 the temperature rose without any preceding 
evidence of a chill to 104° F. The blood at this time contained 
numerous quartan parasites and also some tertian, though the 
former predominated. The blood was examined every two hours 
and no quinine was given. Two hours after the rise of tempera- 
ture the blood contained many large non-pigniented tertian para- 
sites and only a few young quartans. Two hours later both varie- 
ties were abundant but the quartan probably predominated. At 
the next examination, two hours later, the number of tertians was 
small. The temperature rose three times on consecutive days 



NERVOUS AND MENTAL CHANGES IN PELLAGRA 245 

and at the time of each rise the quartan parasites predominated; 
the tertian while present were found in only very small numbers. 
After the third rise there was an interval of moderate temperature, 
with a rise on the fourth day to 105° F. Again, on the fifth 
day, after an interval of irregular temperature, there occurred 
another rise to 105° F. At this time quinine was given hypo- 
dermically with prompt response. This treatment was followed 
by iron and arsenic. For a period of forty days there was no 
fever, no skin lesions, and a decided improvement in the mental 
condition. After this interval of normal and subnormal tempera- 



F. 

105° 
104° 
103° 
102° 
101° 
100° 
99° 
98° 


NOV. 
29 30 


DEC. 

1 


2 


3 4 


5 


6 


7 


8 9 


10 


F. 

105° 
104° 
103° 
102° 
101° 
100° 
99° 
98° 


Q & T 




















1 




MAFew 1 




I 






1 il\ 






< 


■&, 


\"l 


iwT 


! 


A 


V 


\ H\ 
















V 


U 








I 




/ 


A 


K 


\ 


V\i 








\ 


j 




i A 


N 












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\J 


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r 










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i 












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Chart II. — Author's Case. (Jour. Am. Med. Assoc, Vol. XLIX, p. 1891. Trans. 
College of Physicians of Philadelphia, 1908.) Combination of Tertian and 
Quartan Malaria in a Pellagrin. 

ture a relapse occurred. It was my misfortune to have been away 
from the city at the time, but I returned in time to secure an 
autopsy. The idea of a relapse was confirmed, as the vessels 
of the brain, liver, and spleen were filled with parasites and pig- 
ment. I was able to find only the quartan organisms. The 
specimens were unfortunately preserved in formalin, which inter- 
fered seriously with some of the histo-pathologic work which was 
desired. Doctor Cotton again did the neuro-pathologic work for me 
and wrote as follows : 



" I was able to get a fairly good stain, enough to make a diag- 
nosis, or rather, no diagnosis, as the cortex showed no reaction 
that could be considered pathologic. The topography was un- 



246 A TREATISE ON PELLAGRA 

altered and the elements of the cortex were not affected by the 
malarial infection. There was probably an excess of pigment in 
the nerve cells, which could be accounted for by the patient's age. 
The blood vessels appeared a trifle thickened, but the fixed cells did 
not seem altered or to have proliferated at all and the vessels were 
not increased in number. There was no evidence of general 
paralysis or other organic affection and no evidence of cerebral 
syphilis. The parasites were very easily seen in the blood stream 
and in great numbers. There was nothing of note in the cord 
and peripheral nerves." 

It is a question as to the origin of this pigment. It seems reason- 
able that it was due to the pellagra. At the Time of this ex- 
amination it was not known that such a disease as pellagra existed 
on this continent and none of us were familiar with any phase 
of it. It seems rather remarkable thai there should have been 
no organic nervous changes in the presence of such definite 
psychical manifestations and especially as the patient had been 
sick long enough for an impression to have been made on the 
nervous tissue. It is interesting to compare this case with the case 
of the negro girl of IT years whose cord presented such definite 
degenerative areas. (See microphotographs and account of this 
case on page 230 of this chapter.) It has been impressed on me 
many times that symptoms which to all appearances had a definite 
organic basis were really nothing more than functional without 
any definite pathology. This fact is well illustrated in the fol- 
lowing case. 

Mrs. C. S., aged 33. Mother of three children. Xo history 
of miscarriage. Hygienic conditions good. Her family history 
was negative. Her previous medical history was negative, except 
for typhoid in childhood. 

About ten years ago, two years after her marriage, she began 
to be troubled with vertigo, fainting, and " a rush of blood to 
the head." These symptoms kept her in bed for nearly two years. 
Her physician was unable to find a cause. At this time there were 
neither intestinal nor skin lesions. She finally improved and was 



NERVOUS AND MENTAL CHANGES IN PELLAGRA 247 

able to resume her household duties. For at least four years she 
has suffered every spring with digestive disturbances ; everything 
she ate caused digestive distress which the patient thought was 
made worse by meat food. Stomatitis was among her many symp- 
toms. She was unable to recall the existence of any erythema 
until the spring of 1909. (These notes are dated October 13, 
1909.) The skin lesions were typical, extending four inches above 
the wrist and were of the dry variety. She complained of burn- 
ing of her hands, and in the lower extremities she suffered with 
itching, stinging, and cutis anserina. Diarrhea was not a very 
distressing symptom. Her heart and lungs were negative. The 
systolic blood pressure was 148. All reflexes were greatly ex- 
aggerated and there was marked ankle clonus. No nystagmus 
was present. She was unable to cross her knees without help, sug- 
gesting a " lead pipe " condition. The pupils were very active 
to accommodation and sluggish to light. This sluggishness was 
more noticeable in the left eye. The patient was given the usual 
treatment with atoxyl hypodermically, but did not improve. She 
was very depressed and emotional, unable to stand or even to 
feed herself. She was so insistent in her demands to go home 
that she was discharged from the hospital and sent home on a 
stretcher, as she was practically helpless. I did not hear from 
her for over a year, when I chanced to meet her physician. Much 
to my surprise the patient was not dead, but had almost entirely 
recovered, and the doctor reported that she had resumed her usual 
household duties and was able to perform any activity that she 
was ever able to do in the days of good health. 

It was reasonable to suppose that a condition of such long 
duration and with such definite symptoms of cord changes should 
have an organic basis. The termination naturally suggested a 
mere functional disturbance. 

In the table of the Illinois State Board of Health for October, 
1909, which is here reproduced, we find a great diversity of the 
reflexes indicating a parallel diversity in pathologic conditions. 
This matter is referred to at this place because of its bearing 
on the underlying pathology. In 56 per cent there was increase 



248 



A TREATISE ON PELLAGRA 



of the patellar reflex; 35 per cent showed exaggeration of the 
biceps reflex; 34 per cent with exaggeration of the wrist reflex; 
48 per cent with exaggeration of the plantar reflex. In 20 per 
cent the biceps reflex was decreased, and in 14 per cent the 
plantar reflex was diminished. The Babinski reflex was present 
in 13 per cent and absent in 87 per cent. A further study of this 
table will show such an intricacy of variations that the cases can- 
not be divided up into two great groups: one with the lesion 
of the lateral tracts, and the other with the lesion of the posterior 
tracts. It will be noted in many instances that there is exagger- 
ation of one reflex and decrease of another. In not a single case 
of this series of one hundred was there an instance with reflexes 
normal throughout. Since the first two years of my experience 
with pellagra this has been my experience with a much larger 
series of cases. As mentioned formerly, in our first experience 
with this disease, the patient died or recovered before there was 
time for any indelible impression to be made on the nervous 
system. Cases will be introduced into the text to illustrate this 
point. In the majority of cases I have been impressed with the 
peculiar variations of the reflexes in the same individual. In 
some instances the reflexes of the upper extremity are exaggerated 
while the reflexes of the lower extremity are diminished, and the 
reverse of this. The reflexes of one-half of the body may be 
exaggerated and of the other half normal or diminished. 

The nervous symptoms of pellagra are affected by the seasonal 
variations, just as are the skin and intestinal manifestations, 
though not to such a marked degree. With each recurrence the 
impression on the nervous system is made more permanent until 
finally there is no further amelioration of symptoms, and it is 
usually at this point that the line can be drawn between functional 
and ors-anic lesions. Tuczek noted that the reflexes niav be in- 
creased up to the point of intense clonic contraction. He also 
reported clonus of the upper leg with flexion on the hip. In 
many instances I have found ankle clonus present. In a series 
of 300 cases Tuczek found half with decided increase of the 
knee jerk up to rapid patellar clonus, even on the slightest per- 



NERVOUS AND MENTAL CHANGES IN PELLAGRA 249 

cussion of the tendon. In from 30 to 40 there was dorsal clonus 
and a decided increase of the tendon reflexes of the upper ex- 
tremity. In 8 cases the knee jerks were wanting; in the re- 
maining, partly weakened and partly normal. Differences in the 
activity of the two sides were frequently noted. In recent cases 
the deviation from normal was greater at the height of the pella- 
grous outbreak. In none of the cases with no knee jerk was there 
a trace of ataxia. With an increase in the tendon reflexes there 
also occurs, in some instances, muscular weakness, contractures, 
and spastic gait very similar to spastic spinal paralysis. The 
Babinski reflex was only recently noted in pellagra. It is said 
that the spinal symptoms are not always progressive and may 
remain stationary. The triad of symptoms, paresis, spastic ap- 
pearances, and increase of tendon reflexes, may remain for years 
without the occurrence of contractures, and according to Tuczek 
even in case of severe damage to the cord regeneration may take 
place. 

The following fatal case with mental disturbances is re- 
corded to illustrate grave pellagra without any alteration of 
reflexes. 

Mrs. A. R., examined July 15, 1909. Housewife. Fairly 
well conditioned. Three children living and well. Family and 
previous medical histories have no bearing on present condition. 
In June, 1908, she suffered from obstinate diarrhea, which sub- 
sided during the following winter, though she did not regain her 
normal tone. Early in July, 1909, the characteristic erythema 
appeared on the forearms. Following the erythema of the hands 
there was bleb formation. Stomatitis appeared with the erythema. 
She complained of globus hysterica and with a constant disagree- 
able taste. The lesions later appeared on the back of the neck 
and the chin. There occurred the vaginitis so commonly observed 
in pellagra. Soon after there was noted a mental deterioration 
characterized chiefly by despondency. She complained of pain 
in the head and eyes, and also of vertigo. The reflexes remained 
normal and the patient died in September, 1909. 

This case cannot be classified with the acute or fulminat- 



250 A TREATISE ON PELLAGRA 

ing, as she had been affected for a much longer time than is the 
course of such cases. It seems remarkable that there should 
not have been some spinal changes indicated by alteration of 
reflexes. 

Mrs. J. P., June 23, 1909. A poorly conditioned woman of 
the farming class. She has three children and had a miscarriage 
at six months in her first pregnancy. One month ago she noticed 
an erythema over the wrist joint, which extended upward and 
also downward. It involved the whole of the back of the hand 
and fingers. The upward extension included the point of the 
elbow. A portion of the forearm lesions were vesicular and in every 
instance symmetry was well defined. Mouth and lips were quite 
sore. One month before the appearance of the skin symptom there 
was noted a profuse diarrhea, which decreased with the appearance 
of skin lesions. At the time of the examination there was noted 
fresh symmetrical lesions on both sides of the neck posteriorly and 
a small area over the upper outer angle of the left eve. The arm 
lesion was the most extensive I have ever seen, covering the whole 
of the posterior surface of the forearm and combining the moist 
and dry varieties. The lips Mere much inflamed. The tongue 
and mucous membrane of the whole mouth were red without ulcer- 
ated areas. There was some salivation. The reflexes were normal. 
It was noted that there was present the usual retardation in re- 
plying to questions. 

Again, in this case, although it was recent, changes in the cord 
would be expected because of the severity of the symptoms. 

Many nervous symptoms have been reported as resulting from 
the action of the pellagrous poison. Among these are mentioned 
by Lavinder and Babcock neurasthenia, hypochondria, neuralgia, 
chorea, sciatica, polyneuritis, meningitis, myelitis, " epilepsy," 
and " tetanus." ISTeusser described a case of amyotrophic lateral 
sclerosis, but such an occurrence must be exceedingly rare, as I 
can find no other reference in the literature to such a condition. 
In this connection the following reference of J. W. Mobley * is of 
interest : 

» Mobley, J. W., Trans. Nat. Pel. Cong., 1910. 



NERVOUS AND MENTAL CHANGES IN PELLAGRA 251 

" In considering the neuro-psychic phase of pellagra, it will be 
expedient to study, first, the two conditions together, without at- 
tention to their strict division into separate clinical entities. In- 
deed, I might say, seldom do we have in Georgia an organic disease 
of the nervous system, of pellagrous origin, without invasion of the 
psychic realm. On the contrary, so intimately associated are the 
two maladies in many of their clinical aspects, that we are often 
perplexed to know which, if either, merits the place of priority 
in occurrence. An illustration will more adequately explain the 
confusion which has arisen in the author's mind as to whether 
a primary neurosis of a non-pellagrous etiology might exhibit a 
secondary symptom complex, simulating the pellagrous syndrome. 
Take, for example, amyotrophic lateral sclerosis complicated with 
insanity, — the two diseases may progress with the preponderance 
of symptoms favoring a spinal lesion as the primary site of in- 
vasion. The mental states may vary from mild confusion to com- 
plete delirium; the reflexes may be exaggerated with a variable 
Babinski and Gordon paradox ; the patient gradually develops a 
sore mouth, with alternating diarrhea and constipation; later the 
skin lesions appear with variable intensity. Have we pellagra with 
amyotrophic lateral sclerosis and insanity as complications, or have 
we insanity and organic cord disease, with a pellagrous complex ? " 

Bassoe of the Illinois Pellagra Commission in a study of nine- 
teen cases made of them three groups : cases where degeneration 
of the pyramidal tracts was probable ; cases of degeneration of 
the posterior columns ; cases with combined degenerations. These 
results were confirmed at autopsy in most instances. 

In a case of my series symptoms occurred which strongly sug- 
gested acute ascending paralysis (Landry). This disease has been 
known to follow the specific fevers, especially in debilitated pa- 
tients. It is not uncommon in typhoid fever to have such a 
sequel. Ross, Neuwerk, Barth, 1 and others claim that it is a 
peripheral neuritis, while Spiller x found in a rapidly fatal case 
destructive changes in the peripheral nerves and corresponding 

1 Osier, Wm, " Practice of Medicine." 1906. 



252 A TREATISE ON PELLAGRA 

alterations in the cell bodies of the ventral horns. He thought 
that some toxic agent acted on the lower motor neurones as a whole 
and explained the absence of lesions in some cases on the ground 
that delicate methods were not used in the study. Buzzard found 
the Micrococcus thecalis in pure culture in one case. There are 
those who claim that the disease is a functional disorder without 
any anatomical basis. At the present Osier * regards the disease 
as an acute poisoning of the lower motor neurones. 

E. H. White, aged 27 years. Observed August 2(3, 1909, in 
the James Walker Memorial Hospital, Wilmington. North Caro- 
lina. He was a prosperous merchant in the Piedmont section of 
North Carolina. He gave a history of alcohol and tobacco to excess. 
In his neighborhood there had been one death from pellagra, and 
there then existed two other eases. He had never had any serious 
sickness before the present trouble excepl measles three years before 
he came under my observation. From this sickness he dated his 
present trouble, as he said he had never been well since that time. 
Since this attack of measles he was constantly troubled with a 
gastric disturbance. On July 15, 1908, the present trouble began 
with nausea and vomiting and pains in his limbs, which he thought 
were rheumatic. Since this time, at intervals of about three week-, 
he has had such attacks, which would last for ten days. In October, 
1908, he was unable to walk or feed himself. In September of the 
same year he first noticed a stomatitis. During this first outbreak 
the only noticeable skin lesion was found over the knuckles and 
was of the dry variety. Although the winter of 1908 was spent 
in Florida under the most favorable conditions that money could 
buy, he continued to have these attacks of nausea, vomiting, and 
rheumatic joint pains at intervals of about three weeks. About 
June 1, 1909, the erythema appeared on the backs of the hands 
and also on the shoulders. The whole of the arms and forearms 
became affected with that peculiar lamellated erythematous con- 
dition which has been described on another page and which I 
count very distinctive of pellagra. The stomatitis had been present 
for nearly a year without intermission. Throughout the whole 

1 Osier, Win., " Practice of Medicine." 1906. 



NERVOUS AND MENTAL CHANGES IN PELLAGRA 253 

year also the bowels had been deranged and the diarrhea did not 
seem to be aggravated by the coming of spring. Two weeks before 
the date of admission he became unable to walk. Vomiting was. 
very persistent, and at this time I learned that two years previously 
he had vomited half a pint of bright red blood, though no definite 
history of gastric ulcer could be elicited. The patient was cachetic 
and had lost about forty pounds since the beginning of his sickness. 

Examination showed the heart and lungs negative. Systolic 
blood pressure was 140 mm. of mercury, and the pulse was 120. 
The biceps and patellar reflexes were absent. The pupils were 
normal. At this time he was unable to walk without assistance. 
The gait was very unsteady and of a shuffling character, no effort 
to raise the feet in taking a step being made. Station was very 
imperfect, and he would certainly have fallen if not supported. 

August 30, 1909. The degree of redness of the patient's mouth 
had greatly increased. He was having six bowel movements in 
the twenty-four hours. He could not stand alone without falling 
at once. By assistance he attempted to walk, but his gait was 
quite ataxic ; his efforts to raise his foot high enough to prevent his 
heel from striking the floor was a failure. He was almost unable 
to cross his knees. All reflexes were abolished except those of the 
eye. Articulation was progressively more difficult until one was 
unable to understand prnch of what he said. There was a red- 
ness of his toes which was more suggestive of Raynaud's disease 
than the erythema of pellagra. The pulse varied from 120 to 
130. Coordination was very defective and seemed to be more 
decided on the left side. He responded very slowly to questions 
and it was difficult for him to comprehend what you desired in the 
simplest questions. The urine at this time was negative. 

September 2, 1909. Transfusion of blood was done by T. M. 
Green, the donor being a healed pellagrin, though a poor sub- 
ject for such a purpose. The patient was stuporous and could 
not swallow without great danger of strangulation. He would 
slowly protrude tongue when told to do so. The stupor was gradu- 
ally deepening. Occasionally he would take a deep breath, but be- 
tween times his breathing was quite shallow. There was inconti- 



254 A TREATISE ON PELLAGRA 

nence of the bowel and bladder. There were indications of a return 
of the erythema of the hands. Pulse 140. Temperature 102 °F. 

September 3, 1909. Stupor was deepening into actual coma. 
He was unable to take any form of nourishment. Eyes were nor- 
mal. At times there seemed to be present a slight nystagmus. 
There was slight twitching of the fingers. He died at 10 : 30 p. m. 
of respiratory failure. 

A later inquiry into his nervous history revealed the occurrence 
a year prior to his admission into the hospital of an attack of 
some form of unconsciousness which lasted all night, and during the 
preceding summer (1908) he was unable to walk for some days, 
and his wife says that his gait and incoordination at that time 
were the same as now. It is very probable that this patient's 
nervous symptoms were functional without any underlying organic 
change. An autopsy could not be procured, much to my regret. 
It will be noted that this description differs from that of Osier's * 
two cases. In these cases there was no involvement of the sphincters 
of the bowel and bladder. It will also be noted in his cases that 
sensory symptoms occurred while none were noted in this case. 
Further, he rather emphasized the enlargement of the spleen, but, 
again, this change was absent in my case. 

A condition which strongly suggests the possibility of ataxic 
paraplegia has occurred in my series of cases. As Marie believes 
that in many cases the distribution of the sclerosis is due to the 
arterial supply and not to a true systemic degeneration, it may be 
reasoned that such an occurrence would not be improbable in 
pellagra where there is supposed by Alariani to be a definite 
arterio-sclerosis caused by the disease. The increase of reflexes 
with ankle clonus, gradually developing rigidity of the legs not so 
marked as in uncomplicated cases of lateral sclerosis, marked in- 
coordination and difficulty in walking in the dark or swaying when 
the eyes are closed, and to some extent the characteristic gait 
which is common to this disease is not an uncommon picture in. 
certain cases of pellagra. One of the cases mentioned on a previous 
page well illustrates this condition. 

1 Osier, Wm, " Practice of Medicine." 1906. 



NERVOUS AND MENTAL CHANGES IN PELLAGRA 255 

The nervous symptoms occurring in pellagra during the early 
stages of the disease are usually of functional origin. The ex- 
ceptions to this rule must indeed be quite uncommon and have no 
basis in the pathologic findings so far made in this country. My 
own experience is that many of the cases even of several years' 
duration are of functional origin. This opinion is based on actual 
pathologic findings, using the most approved technique of modern 
neuro-pathology. 

Among the symptoms of this class more usually encountered are 
headache, chiefly occipital ; pain in the back and in the neck ; 
globus hysterica ; sensations of prickling and formication ; dizzi- 
ness ; general muscular weakness ; uncertainty of motion due 
chiefly to weakness of the lower extremities. There also occurs 
psychical irritability, ill temper, complaint of giddiness and pres- 
sure in the head, disinclination to any form of exertion, and a 
high degree of mental weakness. It will be noted that the only 
distinguishing feature of these symptoms is the general indefinite- 
ness and unlimited number. There is hardly a functional nervous 
symptom which does not occur at some time or other in some type 
of pellagra. In the second stage of the disease the following ner- 
vous manifestations occur : various parasthesias, especially itching 
of the backs of the hands out of proportion to the extent of the 
skin disturbance, itching of the back and occasionally of the lower 
extremities ; burning in the shoulders, epigastrium, feet, hands, 
and arms, which is supposed to be the cause of the tendency of the 
patient, according to Lombroso, to leap into the water; formi- 
cation ; sensations of cold, chiefly in the lower extremities ; globus 
hysterica ; peculiar prickling sensations, more pronounced than in 
the first stage, occurring in various parts of the body ; pain in the 
head, neck, and back, with a tendency to opisthotonus. The psy- 
chical symptoms which occur at this time will be mentioned later 
under a separate head. The motor disturbances are usually mani- 
fested by muscular weakness, chiefly of the lower extremities, 
which may be semi-flexed because of circumscribed paresis of the 
extensors. The observations of Procopiu and Tuczek are identical 
in regard to the motor disturbances. They both mention muscular 



256 A TREATISE ON PELLAGRA 

tension and tonic contractions of both upper and lower extremities. 
This may increase up to the point of tetanic rigidity. In many 
cases there also occurs a tremor of the arms, the head, and the 
tongue. Cramps, convulsive movements of single limbs, and, in 
some cases, pronounced epileptiform convulsions with loss of con- 
sciousness have also been observed. The patient mentioned on a 
previous page had a definite epileptic-like spasm some months be- 
fore his death and his death occurred in such a seizure. It cannot 
be said that the occurrence of epileptiform seizures is a common 
event in pellagra. Out of four hundred cases collected by me 
I was able to find only this one case. 

Disturbances of sensibility occur in pellagra at varying periods 
of the disease. In niv experience the study of this condition has 
been very unsatisfactory, for the reason that the occurrence was 
late in the disease, when the mentality of the patient was such 
that replies to questions could not be relied on with any degree 
of certainty. Marie says that tactile and temperature senses re- 
main intact, but such has not been my experience, as I have seen 
a marked perversion of both in many cases ; but, as stated above, 
I am forced to modify my statements in this particular, owing to 
the inability of the patient to make intelligent replies. Marie 
again states that the sense of pain is diminished, especially in the 
legs, and that muscular sense is normal. 

Tuczek stated that the gait in pellagra was paralytic usually, 
occasionally paralytic-spastic, but never ataxic, even in cases with 
an absence of tendon reflexes in the lower extremities ; that static 
ataxia is occasionally mentioned; that incoordination of motion 
is mentioned only very occasionally and then only in the upper 
extremities; that symptoms suggestive of intention tremor have 
been observed ; unilateral ptosis has occurred in a number of 
cases. 

Marie with Roneoroni studied the electric reaction of the mus- 
cles and nerves in four cases. The patients had been for. some time 
in the hospital "of Turin and three of them were in good physical 
condition. The reaction of degeneration was not present and there 
was neither quantitative or qualitative deviation from the normal. 



NERVOUS AND MENTAL CHANGES IN PELLAGRA 257 

The electrical excitability was less in one than in the others and 
was attributed to malnutrition. Tie said that this was interesting; 
for differential diagnostic purposes from polyneuritis, progressive 
muscular atrophy, amyotrophic lateral sclerosis, transverse mye- 
litis, and other conditions. 

Among the parasthesias was mentioned a sensation of burning 
which may occur in any portion of the body. It must not be con- 
fused with the violent neuritic pain which is so commonly com- 
plained of by the patient. This pain occurs chiefly in the palms 
of the hands and soles of the feet and is oftentimes a most dis- 
tressing symptom. In my experience it has proven of grave prog- 
nostic portent. This pain is often so severe as not to be influenced 
by the full dose of morphine administered hypodermically. 

Mrs. T. E., seen through the courtesy of W. F. Hargrove of 
Kinston, N/orth Carolina, 27 years of age. She had no children 
and no history of miscarriage. Her general hygienic conditions 
were good. Family and previous medical histories were negative. 
Admitted on July 9, 1909. In June, 1907, she had an attack of 
symmetrical erythema on the backs of both hands and forearms, 
no stomatitis, but a slight diarrhea. In 1908 the outbreak was so 
slight as not to be well recalled. Late in March, 1909, erythema- 
tous lesions appeared simultaneously on both thumbs. In April the 
lesion involved the greater portion of the hand and a few weeks 
later blebs appeared. About this latter time a stomatitis ap- 
peared and the bowels became severely affected. There was con- 
siderable tenesmus with the diarrhea and sometimes the move- 
ments contained blood. About the middle of May neuralgic pains 
appeared in the feet, but there was no erythema in this part. This 
pain was chiefly in the ball of the foot and she described it as feel- 
ing as if some one was chopping it with an axe. The pain was 
so violent as to require an opiate. About June 1 the lesion ap- 
peared on the back of the neck unattended with bleb formation or 
pain. There was a slight lesion on the upper lids. There was no 
tremor, no clonus, and station was good. The reflexes were exag- 
gerated to a very marked extent. Her mental state was good. 
The pain in the feet was never relieved and the same pain ap- 



258 A TREATISE ON PELLAGRA 

peared in the upper extremities. The doctor wrote me that up to 
the time of her death she continued to suffer violently, opiates 
having no appreciable effect. The case impressed me as being of 
the mild type and her death was a surprise. The only symptom 
that seemed to be of any importance after the diagnosis was made 
was this pain. 

These neuralgic pains are a frequent occurrence in my practice, 
and I have often wondered why so little is said of it in the 
literature. 

The vertigo of pellagra is a symptom which is referred to by 
all writers and counted of great diagnostic value. It often pre- 
cedes the appearance of any other definite symptom. It is usually 
counted a neurotic symptom though some thought it was caused 
by a gastric anomaly of secretion. This symptom is not of so great 
value in the United States as in Italy. I usually elicit it but it 
has certainly no pathognomic value, and as it occurs in so many 
other conditions I do not think it is entitled to so much promi- 
nence. Often the patient complains of a " queer feeling in the 
head/' and it is especially noticeable how rapidly this condition 
improves with arsenic medication. 

The tremor of pellagra is often referred to in the literature 
and has been observed by the students of the disease in the South 
very often. It was noted by Strombio, the elder. Belmondo spoke 
of a tremor like that of the intention tremor in disseminated 
sclerosis, which is more marked in the upper extremities, espe- 
cially in the fingers. Occasionally tremor of the head and tongue 
occurs. This tremor in my experience is more like a condition 
of clonic spasm than a real tremor. This clonic tremor is very 
coarse and unlike anything seen in any other condition. It is 
largely confined to the upper extremities, and I have never seen 
anything about it that suggested intention tremor. It seems to 
be much more often seen in women than in men. 

The occurrence of contractures was mentioned on another page. 
Such a condition has not occurred in my experience. Marie says 
that in the movements and attitude of the pellagrous there is a 
tendency to certain contractures. When these patients rise it is 



NERVOUS AND MENTAL CHANGES IN PELLAGRA 259 

done with considerable difficulty. When the arm is extended it 
remains rigid and semi-flexed; sometimes the limbs are tightly 
drawn up. Often grotesque attitudes are assumed. Marie says 
that they squat down with the knees pressed against the chest and 
abdomen and cling to some object with hands or feet or even with 
the teeth. The result is often stigmata and characteristic deformi- 
ties. I have often seen these poor wretches drawn up in bed with 
the head covered by the bed clothes as though in mortal terror of 
being seen. The whole body is intensely rigid and any effort to 
correct the strained position of the patient is followed by an im- 
mediate resumption of the former position. 

There occurs in pellagra, though rarely, what Marie calls a 
partial chorea : that peculiar tendency to run in a straight line. 
It is said to occur more frequently in the morning hours. He says 
that there is also something which reminds one of epilepsy with 
ambulatory automatism. In typhoid pellagra the same writer 
observed contractures alternating with clonic spasms of the face 
and extremities suggesting electric chorea or tetanus and said to 
be aggravated by sensory impressions. It is often mentioned by 
the Italians that pellagrins have a tendency to fall backwards, 
forwards, or sometimes to the side as a result of the above-men- 
tioned vertigo and sudden tetanic movements. Marie says this 
is what the people in pellagrous districts mean by pellagrous 
spells. Calderini reported this occurrence in 75 per cent of men 
and 77 per cent of women. 

We read in Lavinder and Babcock's translation of Marie's 
work: 

" General tonic spasms with trismus and subsultus appear under 
the influence of light tactile stimuli in many patients, just as in 
experimental animals. The opening or shutting of a door, the 
noise of an electric bell will sometimes provoke these spells. In 
one case tetanic rigidity persisted even during sleep, with eleva- 
tion of temperature to 39 and 41° C. As long as they walk and 
eat patients have the sensation of a cord stretched across the back 
which draws them forward or to the side and they bend in that 



260 A TREATISE ON PELLAGRA 

direction. These attacks, because light and fleeting, might be 
called opisthotonic, emprosthotonic, and plenrosthotonic tetanus. 
' The convulsions often have the appearance of tetanus,' says Alli- 
oni. Often contractures of flexion and extension result from 
them ; some of them extend their arms in the form of a cross and 
remain rigid from four to six minutes ; others remain whole weeks 
with the limbs extended and rigid, like katatonics; others have 
the sensation of a force which draws them by the head or obliges 
them to stiffen out the legs (Xardi)." 

In the series of cases studied by A. Gregor the findings of Ton- 
nini regarding the tendon reflexes were confirmed. These changes 
were: increase of the tendon reflexes, increase of the mechanical 
muscular excitability, tremor of the fingers, rigidities and spasms 
of the lower extremities, spastic gait, diminution of the tac- 
tile, thermal, farado-cutaneous sensibility, paresthesias, ataxia 
of the lower, in rare cases of the upper, extremities, and Rom- 
berg's sign, lie emphasized the presence of muscular spasm 
and records the presence of tonic spasms in the terminal stage 
of the disease. He gives the following history illustrating this 
condition : 

The patient lies stiff on his back, elbow and wrist joints flexed, 
as well as the knee joints, and the feet show plantar flexion. There 
is present in all extremities a severe form of spasm and a complete 
extension is impossible. He perforins slowly extreme rotation 
and the arms are abducted and adducted in a jerking manner, 
^lien drinking motions are made in the presence of the patient 
he makes a jerky effort to raise his hands to his mouth, appar- 
ently resisting the involuntary contractions of the hands and 
arms, but finally he is successful in bringing the wrist joint of 
the spasmodically flexed hand near the mouth. The head is held 
in maximum spasmodic lateral rotation. On the next day jerking 
movements of the large muscle bundles of the lower portion of the 
face and of the forearm were observed. Gregor also observed 
clonic spasms in a female patient. To quote Allemann's transla- 
tion of this article of Greffor : 



NERVOUS AND MENTAL CHANGES IN PELLAGRA 261 

" In the morning the patient lies on her back, the eyes are closed, 
the upper arms are adducted, the forearms flexed at an angle of 
90°, which positions are kept fixed. In the region of the left lower 
facial nerve, I observed fine tremors which do not lead to any 
motor effects, also others, coarser ones, which draw the whole half 
of the mouth downward. The same tremors are also observed, 
though less severely, in the right lower facial nerve. The mouth 
is drawn a little to the left. Similar tremors of fine and coarse 
muscle fibers are also noticed in the sterno-cleido-mastoid and pec- 
toralis on both sides. The upper arms perform adductions and 
abductions in a jerklike manner and the lower arms flexions and 
extensions. The thumbs are now and then adducted in spasms, 
the fingers flexed. Similar spasmodic movements are also ob- 
served in the lower extremities. There exist also spasms in smaller 
bundles of all muscles of the extremities. 

" Passive movements find everywhere spastic resistance. The 
pupils react promptly to light and are of equal size, reflexes in- 
creased; spontaneous defecation and micturition. The patient 
does not respond when called by name, the face is distorted when 
pain is inflicted; the condition slowly disappears until the next 
day. 

" In contrast with the first-mentioned case, no severe nervous 
disturbances were observed in this patient either before or after 
the appearance of the clonic spasms; on the other hand Tonnini 
observed clonic spasms only in the third stage of pellagra. Neither 
did typhoid pellagra exist in this case, a condition in which the 
patients are inclined to clonic convulsions (Lombroso). 

" I would also mention that in some cases a paresis of the lower 
facial nerve was observed which in one case developed during her 
stay at the hospital. The occurrence of this disturbance is also 
remarkable as it is of value in the question of the relations of 
pellagra to progressive paralysis considering also the pupillary 
disturbance in the third stage. While Baillarger once tried to 
prove, in opposition to Verga, that pellagra may be followed not 
only by mania and melancholia, but also by progressive paralysis, 
the question is rather analogous to that of specific alcoholic paral- 



262 A TREATISE ON PELLAGRA 

ysis: Is there a form of paralysis produced solely by pellagra? 
The question is answered affirmatively by Pianetta, negatively by 
Verga. 

" Among the anomalies of sensibility, the disturbances of farado- 
cutaneous sensibility are strikingly marked, on account of which 
I tried to determine it exactly on the skin of the forearm, which 
according to Tonnini is especially non-sensitive to faradic irrita- 
tion. In all cases examined, I found extreme weakening of sensi- 
bility." 

I have noted the clonic spasms recorded by Gregor, but, con- 
trary to his expressed view, I count them a part of typhoid pel- 
lagra which he says was absent in his case. Certainly this symp- 
tom has never occurred in any case except a short time before the 
termination in death. I have never seen it in the acute or fulmi- 
nating cases even though they proved fatal. It is a very character- 
istic manifestation which once seen is never forgotten nor con- 
fused with any other condition. It is so characteristic that more 
attention should be paid to it, and its value both from a diagnostic 
standpoint as well as from the viewpoint of prognosis should be 
more emphasized. 

It will be seen then that the manifestations of pellagra on the 
spinal cord are even more diversified than the cord manifestations 
of syphilis, and it is impossible to describe any one condition of 
the cord which is distinctive of it. This is a fact of great impor- 
tance especially in pellagrous sections or in patients from such 
localities. The neurologist must add this possibility to his list in 
taking histories of patients with spinal cord symptoms. 

It will be seen that the changes in the cerebrum in pellagra are 
not so definite even as the changes recorded in the cord, though it 
must be acknowledged that too little neuro-pathologic work on the 
cerebral cortex according to the most improved modern methods 
has yet been done, especially in the United States. At this time 
we can only say that in many cases manifesting marked psychical 
disturbances the pathologic changes were absent or insufficient 
to account for them. 



NERVOUS AND MENTAL CHANGES IN PELLAGRA 263 

The time of the appearance of mental symptoms in pellagra is 
subject to all possible variations. The reader will recall the case 
of the grocer who was supposed to be suffering with a symmetrical 
gangrene of the skin due to malaria and which was later found 
to be pellagra. In this case the mental disturbances antedated 
all other symptoms by many weeks. On the other hand I recall 
the case of an old unan who told me that he had been pellagrous 
for forty years and yet he was able to make his living as a laborer 
and manifested absolutely no symptoms of the disease from the 
mental standpoint. This brings up the very interesting question 
as to whether the numerous cases of pellagra in the insane in 
southern institutions were of pellagrous origin or were instances 
of the engrafting of pellagra on a preexisting mental disorder. 
It also calls for an answer to the query as to whether or not the 
insane are peculiarly susceptible to pellagra. I have in mind the 
case of a woman who was an inmate of an insane institution for 
four or more years before the first symptom of erythema ap- 
peared. Her brother later developed the same type of insanity 
but the full picture of pellagra never developed ; his distinctive 
symptoms being merely stomatitis and diarrhea, which may occur 
in other forms of mental disorder. It is likely that many cases 
of pellagra have been overlooked on account of the mildness and 
very limited character of the erythema, and again, it is not im- 
probable that many of the cases observed in some of the American 
insane institutions presenting erythematous lesions of the hands 
and diagnosed dementia paralytica were truly pellagrous. We 
recall the opinion of Siler that pellagra occurs in practically all 
the insane institutions in the United States. 

There is nothing distinctive of the mental symptoms of pellagra 
and the picture varies almost as much as did the cord symptoms. 
The only one characteristic which I have uniformly noted is the 
depressive type of psychosis. This observation is borne out by all 
observers. Delusions of grandeur never prevail, but delusions of 
persecution are exceedingly common. It is said by most writers 
that these patients are never dangerous, and as a rule this has 
been my experience though an exception will be later noted. Grief 



264 



A TREATISE ON PELLAGRA 



over imaginary sins and short-comings has predominated the 
psychic picture of so many of my cases that I have often been 
tempted to count it of considerable diagnostic value. 

In the earlier cases which occurred in the United States, as 
would be expected, psychical symptoms did not play any great 
part and many patients died without manifesting the slightest 
evidence unless a general depression is placed in this category. 

Gregor's first classification is called neurasthenia. My cases 
have manifested symptoms of this condition as a part of a devel- 
opment of a more serious state. He says that in this group he 
places patients who manifest symptoms of headache, pain in the 
gastric region, pressure in the head, vertigo, lassitude, depression, 
a sense of unrest which is stressed by Tuczek, anxiety which may 
be increased to phobia, fear of something undetermined which is 
threatening, a sense of bodily and mental incapacity, and of illness. 
The patient appears well behaved, not disturbed intellectually but 
incapable of mental or bodily activity of any sort. He claims that 
the process of association is decidedly disturbed and the simplest 
questions are often answered only after long hesitation. I have 
been deeply impressed with this peculiarity of these people. Some- 
times this retardation is so great that the one asking the question 
will almost forget it before the reply comes in a drawling, stolid 
fashion, reminding one of a very deaf person who, not hearing but 
a portion of the conversation, continues on the subject heard long 
after the general conversation has moved on. The tone in which 
these replies come reminds one of that peculiar type of utterance 
heard so often in opium habitues. The spirits are depressed and 
the patient appears anxious. Hypochondriacal notions are often 
recorded which Gregor says receive new stimulation from the 
subjective troubles from the consciousness of being pellagrous 
and from their own experience of former serious sickness. There 
is sometimes motor unrest and a constant tendency to be on the 
move, but the physical condition often has a greater tendency to 
produce motor impediment and the patient becomes markedly 
apathetic, not being willing even to get up for a movement of the 
bowels. Stolid indifference is also a characteristic of these pa- 



NERVOUS AND MENTAL CHANGES IN PELLAGRA 265 

tients. This indifference manifests itself in several ways. A 
mother will become utterly indifferent to her child even though it 
be an only one. A man who had been hitherto most careful of his 
dress becomes most untidy, not from a change in disposition per 
se but because of this lethargy. 

There seems to be a kind of sensitiveness on the part of the 
victims of pellagra and they will conceal the fact of their affliction 
to the very utmost, as though it were a disgrace of which they were 
ashamed. This peculiarity is really a neurasthenic manifestation 
according to my observation. It seems to be more pronounced 
among the Italians than in this country. 

Of the 72 cases studied by Gregor 7 belonged to this neuras- 
thenic group. 

Gregor's next subdivision is acute or stuporous dementia. Of 
his series 10 were thus classified. This group includes mild cases 
which are merely exaggerations of the neurasthenic class. All 
the symptoms above referred to are accentuated and the psycho- 
motor disturbance is increased to stupor. Such patients lie for 
weeks in an apathetic state and in order to impress them with a 
question it is necessary to repeat it with marked intonation, as 
Gregor says, and the reply is made with great effort in the simplest 
terms or no answer at all is heard. I have often noticed that in 
those cases where no answer is given there is an expression of in- 
telligent appreciation of what is desired of them but a motor ina- 
bility prevents the reply. Requests to do anything are followed 
out with hesitation and effort and the resulting action may be 
stopped in its first phase, or the request may be forgotten before 
the execution is completed. This is very characteristic and was 
well illustrated in the case detailed on page 243. Gregor says that 
these patients are fairly well oriented and that the psychic activity 
is often revived for a short time. In the height of the disease 
orientation is sometimes definitely disturbed. Illusions of varying 
nature were present in all of my cases reaching this stage of pel- 
lagra but there was an absence of any distinctive quality. There 
is usually noted that lack of confidence in oneself which is almost 
a timidity and which is so often noted in psychasthenia. It is 



266 A TREATISE ON PELLAGRA 

a notable fact that these people possess a consciousness of their 
psychic deficiency as well as a general hypochondriacal point of 
view. This is as true in my own experience as it was in Gregor'-. 
The following letter was received from a patient who was on 
the border line between this acute dementia of Gregor and his 
neurasthenic group. The patient called at my office but had noth- 
ing to say. On leaving, however, she handed me the following 
letter, which was written clearly and connectedly. 

"Dear Doctor, — I guess you will think I am foolish but I 
am going to tell you my story, of all my sufferings of this past 
summer. I shall tell you nothing but the truth, so help me Heaven. 
Now, I was always of a happy disposition, always looking mi the 
bright side of everything, always had a Laugh and a joke for all; 
not what you find me to-day, a wreck of my former self. Well, to 
my story, of how I have watched the development of this disease, 
calmly, for I knew I was coming to you for treatment if not cure. 
Last April I had a terrible fever, bad trouble with my bowels, and 
nothing could be clone that would cure me of all this trouble. I 
was sick this way for several weeks and could eat nothing; my 
mouth, throat, and stomach seemed to be mi fire. Along in April 
the eruption appeared on wrists, hands, and throat. "Well, I seemed 
to get better of the dysentery and was feeling pretty well, but the 
eruption spread rapidly, soon getting to the elbows. . . . The 
eruption appeared again and soon spread more rapidly than ever ; 
a new spot appearing above each elbow and on each shoulder, I 
did not treat it right off and it soon covered my arms, neck, and 
shoulders, burning fearfully. 

" In August Dr. X. began treating me and to look back and try 
to remember the treatment I welcome the disease. Pellagra causes 
insanity and awful suffering but is slow in its progress, but I 
found this treatment awful in its rapidity in causing insanity, as 
you will see by the following, my recital of his treatment. When 
I started his treatment I thought I was a sick woman, but when 
I left him I was one hundred times worse than when I began. 
Of course my memory has been failing me a long time and I was 



NERVOUS AND MENTAL CHANGES IN PELLAGRA 267 

somewhat giddy when I began with the doctor. Well, the first 
week he gave me a lot of things to take, among which was something 
that was to be taken three times daily and increased just one drop 
a day until he told me to stop. The first week, also the second, I 
thought I was better. The first hypodermic was in my arm. I felt 
no effect of it, but the next was in my hips. The second injection 
made me feel like a new woman. I had not a care in the world, 
or it seemed that way. The next time I went the injection made 
me so sore and stiff until I could hardly walk. I could not lie 
on that side for several days. The next time I went to him I asked 
him if it was the same kind of injection, he said it was, I told him 
how it affected me, he said it belonged to act that way, so I kept 
going to him every two nights, getting worse each day. Oh, I 
shudder now, as I try to think and my mind gets more confused 
as I try to tell you how I suffered. God in his pity for my igno- 
rance saved my reason. I would have gone insane, anyway, if I 
had not asked God to help me until I could come to you. Before 
going to the doctor I had good nerve and good will power, so I did 
not worry for I knew I was coming to you, and I would bear all 
patiently. I lost most of my weight after this treatment. Any 
of my friends will tell you that. Well, after a while I began to get 
more giddy than ever ; I seemed to be stepping down, down, down ; 
muscles seemed to contract, lost nearly all power of my fingers and 
wrists and arms. Every joint I had seemed to be getting para- 
lyzed; I had to grasp anything I could find to keep from falling, 
so giddy was I. My whole brain seemed to grow more blank after 
each treatment. My head had a roaring sensation, and in about 
four weeks time, I had forgotten home and friends, even my God 
was forgotten. 

" I could not eat, he said he did not wish me to eat much. The 
dysentery began on me and each time I went to him I told him he 
was killing me ; he said I would be soon well. ... I knew I was 
an idiot for taking another treatment of him but my brain was 
awfully weakened, and I kept going, getting worse each time. 
One night my left ear seemed to burst, such a roaring, stewing 
sensation in it. My eyes were almost ruined. I could not recog- 



268 A TREATISE ON PELLAGRA 

nize my husband fifty yards away. I could not read a line, the 
letters seemed to all mix and dance before my eyes and I grew so 
sick and nervous as I vainly tried to read; I would be quivering 
all over and my head would seem to be rocking back and forth. 
I seemed to be falling on my face when I walked. My arms would 
seem to try to come to my chest and fold there. I had to keep 
them straight. My knees were in the same awful fix. It seemed 
like I was going to fold up, every muscle contracted, and I felt like 
I was being drawn to the earth to rise no more ; two large sores 
came on my neck and one under my left jaw; also one above my 
left brow and one on the edge of my forehead, all on the left side 
of my face. He said it belonged to be that way, and gave me 
sodium phosphate salts, effervescent. Oh, that ruined my mouth 
and stomach. Made the hemorrhage worse, gave me awful dysen- 
tery. I thought I must die the last three weeks he treated me. I 
could hardly dress myself to go to the doctor. 

" My husband had to bring the buggy to the door and lift me in 
many times. My right ear had the sound of guns firing in it, low 
muflied sounds; that horrible itching, burning in my head was 
ever present, getting worse each day. I could only stand twenty- 
four drops of that poison he gave me to take, I took it until 1 had 
taken eight drops three times on the last day, told him I could not 
take more at that time. The hemorrhage (menorrhagia) was so 
bad I must die. Oh, I was in the most awful condition. My mind 
grows dark as I think, but. the more I went to the doctor the worse 
I grew, my mind seemed to be gone, my brain was in the grasp of 
some awful something. . . . Well, I was so numb and paralyzed 
and foolish and kept getting worse all the time. I seemed to forget 
everything, my saviour as all else in this blind, awful suffering. 
... I hope you can save my reason, I feel like an idiot but hope 
you, with the help of the most High, will make me like I was before 
taking this medicine, yes, even that clear-minded. ... I have 
fought this madness each minute, saying I would not go insane. 
. . . My brain would grow so dark that I forgot god and family, 
forgot everything save this awful despair. I would have awful 
times of weeping, and that saved my reason, I think, as my mind 



NERVOUS AND MENTAL CHANGES IN PELLAGRA 269 

would clear for a few days, but settled back to the same old way. 
I have had two spells of weeping since being here, but I know I 
am better." 

The fixed idea of this patient that she had not received the 
proper medication was, of course, absurd. I think she would gladly 
have died if she could have had the satisfaction of knowing that 
the physician had caused it. She was most insistent in her en- 
treaties that I would acknowledge that he had done her harm. 
As she improved this peculiar mental phase somewhat subsided, 
and now she never refers to it at all, though it is not probable that 
she has entirely recovered from her unreasonable prejudice. 

This same patient later wrote from her home the following: 

" And I must tell you the shameful truth, that I only crave such 
things as earth and ashes, charcoal, and such things that a human 
should not eat. I never gratify my depraved appetite. Have had 
this abnormal craving for the past year. N/ow, please do not laugh 
at all this for it is true and I camiot help it, but I thought you 
should know. I think the worst symptom I have is that dreadful, 
creepy, itchy burning sensation in my ears and scalp. I can toler- 
ate all the burning and the other bad feelings I have, but this last 
I 've mentioned makes my brain feel so queer and confused and 
idiotic. ... I dislike to air my troubles to any one and do so 
as little as I possibly can." 

The home of this patient is in the very heart of the hookworm 
section and I am inclined to think that her statement of a vicarious 
appetite is purely suggestive, brought about by the lectures and 
demonstrations of the Rockefeller Commission for the Eradication 
of Hookworm Disease. It is not at all improbable that she might 
have really had the sensation complained of, though in many con- 
versations she never made any reference to it. Certainly she was 
a typical victim of the hookworm infection. Hypochondriasis was 
very marked and she would never tire of telling of her peculiar 
sensations. She never developed the lethargy and indifference so 



270 A TREATISE ON PELLAGRA 

often noted but, on the other hand, she was always very active 
mentally as well as very sensitive. Fear and dread of insanity was 
her constant plaint. A letter of only a few days ago announces a 
fresh outbreak and I am surprised that she seems to be taking it 
very philosophically and does not refer to insanity. Her mental 
condition has greatly improved during the winter as has her physi- 
cal condition, and my last note records a gain of twenty-three 
pounds since last November when I first saw her. 

In many cases there is a very gradual development of the stu- 
porous condition. In these cases Gregor states that there is a dis- 
turbance of psycho-motor activity without vivid mental disturb- 
ances. It is further stated that some patients recognizing their 
mental unfitness apply for admission to the insane institutions. I 
have never experienced this, but it is no uncommon thing for 
them to acknowledge their insanity though the expression is usually 
of a fear of its subsequent development. There is often seen a 
gradual development of an " affectless stupor " which is followed 
by a return to their former mental condition. In some cases 
psychic impediments are said by this same author to develop in a 
relatively short time. The feeling of mental insufficiency, as in 
the above-mentioned case, is apt to have a very melancholy aspect 
and in some instances there may be manifested suicidal tenden- 
cies. It is also noted by Gregor that severe cases may assume tem- 
porarily katatonic symptoms of posture and motion stereotypies. 

Tanzi noted disturbances of memory in this group but Gregor 
says weakness of memory is not a characteristic of acute pellagrous 
dementia and that in convalescence memory readily returns, deter- 
mining that the supposed disturbance of memory was really due to 
difficulty in performing psychic processes. 

Melancholia is the usual mental disturbance in pellagra, and it 
is said that with the improvement in the physical condition there 
will be a corresponding improvement in the mental state. Such 
has usually been my experience with a few exceptions. One of 
these exceptions is the case of a woman who has not suffered an 
outbreak for so long a time that she is counted well of the pellagra 
but she insists that she has only a few more days to live and has 



NERVOUS AND MENTAL CHANGES IN PELLAGRA 271 

regularly sent for one of her children once a week for many months 
in order that he should be present at her death. Tanzi considers 
these cases of melancholia to be really a mild form of amentia. 
Gregor counted stupor to be an unfavorable prognostic sign. 

Of this group of acute (stuporous) dementia Gregor had ten 
cases of his series of seventy-two. 

Gregor's third group, of which he had thirty-two cases, is the 
amentia or acute confusional insanity. He says that they were 
long continued with a tendency to remissions and intermissions. 
There is first a period of varying length manifesting symptoms of 
a neurasthenic character, followed by terrifying hallucinations to 
which is added violent motor excitement. According to Gregor 
delirium was followed by stupor or the stupor was interrupted by 
delirium. He says the patient sees the house or village burning, 
enemies coming, wild animals attacking him, and the devil ap- 
pearing; that more rarely there is a quiet, dreamy state and the 
heavens open and the Lord appears and in imagination they re- 
turn to the scenes of their daily life. There occurs phenomenon of 
motion in connection with hallucinations. When secluded they are 
prone to move about and become noisy. The period of excitement 
lasts from a few hours to several days. These outbreaks may be 
followed by long intervals of mental and bodily quiet. Stupor 
may occur but there is only slight disturbance of orientation. 
Later in the course of the disease they are said to pass into a de- 
lirium of the same character as seen in typhoid fever or menin- 
gitis. In the presence of diarrhea added to this mental state, 
Gregor finds his conception of typhoid pellagra. Hallucinosis is 
said to offer a decidedly favorable prognosis for the first attack. 
Further it is stated that dementia does not always ensue after a 
severe initial attack. The development of katatonic symptoms, 
which is more apt to occur in juvenile cases, makes the diagnosis 
more difficult. 

Gregor's fourth classification was that of acute delirium, and 
of this group he reported two cases out of his series of seventy-two. 
This class is distinguished from the third or preceding group by 
an exaggeration of all the symptoms of that group. There occurs 



272 A TREATISE ON PELLAGRA 

a condition characterized by hallucinations, motor excitation, and 
a shorter course than the preceding which ends in death. These 
symptoms are said to occur in some instances without the bodily 
signs of pellagra though the two usually occur together. Except 
for an absence of a rise of temperature the second, third, and 
fourth groups of Gregor's classification are said to resemble the 
mental symptoms of acute infectious diseases and for that reason 
are arbitrarily placed in a classification under the infective exhaust- 
ive psychoses. 

Gregor's fifth group, designated katatonia, is so different from 
my own experience that I quote the whole : 1 

" The katatonic condition occurs with acute somatic pellagra. 
Here, considering the concurrence of acute somatic and psychic 
pellagra, we must assume a pellagrous intoxication as to the causa- 
tive factors, as in pellagrous neurasthenia. Many patients show con- 
sciousness of their disease. Hallucinations may precede this con- 
dition. Excitement, stereotypy, wild jactitation and verbigeration 
are common. The katatonia cases pass rapidly into dementia. 

" Of the cases of the fifth group, the majority belong to the 
katatonia subdivision from the symptoms, course, and termination. 
In all three cases (females) excitation occurred, ending with stere- 
otypy, jacitation, and verbigeration. The patients did not show 
marked effects. In one case, hallucinations preceded the condition. 
In all three cases, the transition into dementia was rapid, in which 
posture and motion stereotypies, impulsive actions, and talkative- 
ness were observed. In one case, these symptoms were followed 
by a permanent negative phase. In another case, besides many 
posture and motion stereotypies, interchange of negativism and 
flexibilita cerea was observed. In one case, the katatonic symp- 
toms were marked from the beginning. A male case showed on 
admission to the hospital katatonic excitation, and after a few 
days a remission followed by another katatonic phase. 

" Six of these cases ended in dementia more or less rapidly, 
although remissions may occur." 

1 "Pellagra and the Psychoses," by J. W. Babcock. Am. Jour. Insan., 1911. 



NERVOUS AND MENTAL CHANGES IN PELLAGRA 273 

The sixth group of Gregor is the anxiety psychoses. Of this 
group he had three cases. He says that the violent, fluctuating 
anxiety effect, the motor unrest, the anxiety ideas, and the " pho- 
nemes " completing them, determined the diagnosis. It is com- 
plicated, however, by extraneous features. There is shown a sense 
of insufficiency, and the victim appears stuporous in the intervals 
between attacks resembling cases classified under the second and 
third groups. Mental weakness increases after the anxiety attacks 
have disappeared. Psycho-motor weakness alternates with vio- 
lent anxiety effects and vivid motor unrest. Temporary ideas of 
persecution and sin followed by stupor were observed by Gregor. 
One case of this group was typical depressive melancholia. 

The seventh and last group of Gregor was manic-depressive in- 
sanity and two of his cases were thus classified. One showed the 
condition of mania arising from subjective pellagrous troubles 
while in the other the mania was followed by a distinct stupor. 

The classification of Mobley is as follows : 

( 1 ) Acute intoxication psychosis, with jDsycho-motor suspension, 

(2) Infective-exhaustive psychosis, with psycho-retardation or 
excitation. 

(3) Symptomatic melancholia, with psycho-motor retardation. 

(4) Manic-depressive, with psycho-motor retardation or excita- 
tion. 

The following correspondence from a man whom I had known in 
college is interesting. He was a school teacher and well educated. 
Many of the letters received from pellagrins would show even 
better the mental states but for the fact that the majority are not 
well enough educated to express themselves in anything like a nor- 
mal manner, and again at the time of marked mental change there 
usually occurs sufficient motor disturbance to interfere with writing. 
The character of the handwriting itself shows early tiring. The 
letter reproduced on a previous page of this chapter was written 
by an educated woman also. In the beginning there was no error 
but it will be noted that very soon mental exhaustion manifested 
itself in carelessness in punctuation and in failure to use the capital 
letter in speaking of the Deity. 



274 A TREATISE ON PELLAGRA 

" I have a dark feeling day and a bright one succeeding each 
other. I feel on my better days that I shall soon be well. I have 
many optimistic thoughts. On my darker days, my thoughts are 
pessimistic and it seems to me that my case cannot be cured. This 
better and worse day has been true generally but not always as 
sometimes I have had two bright days together. 

" All of that tickling and prodding feeling up and down my 
spine has now ceased, and I no longer feel so much head swimming. 
My thoughts wander or move slowly and are not capable of concen- 
tration to any great extent. I am improving in this matter. This 
is the part especially that I want to improve right soon as I think 
I will when the medicine has acted freely. . . . Truly, I did not 
take the case so seriously until the last day or two. I see that it 
is certain that I shall give up my school work and move back on 
my farm by January next. ... I would like to have space to 
write you fully of the terrible head swimming and dreadful 
gloomy feelings that I have experienced. Mainly all these feel- 
ings have passed off now. Somehow as before stated I cannot fully 
apply my thoughts yet. You may know I am thinking of the 
awful death ahead of me and the motherless children that I shall 
have to leave. Of course I want to think that I will live a few 
years." 

Following this letter in a few days the following was received 
from the same patient. 

" Deak Sir, — I wrote you some time ago as to my sickness. 
Now it seems that my blessed reason is returning and I write 
you more of my illness. 

" Doctor, please tell me whether committing sin or moral 
wrong Avill bring on pellagra. Somehow my affliction appears 
to be of Divine infliction. I want to get well. I am willing to 
confess any wrong if necessary. As only a very slight sample 
of my ungodliness is embraced in the letter to Miss X., I am 
sure you will understand my letter to her well enough to apply it 
in any and all ways for the best. I feel somewhat that I may 



NERVOUS AND MENTAL CHANGES IN PELLAGRA 275 

recover. God's people are praying for me. The above is my own 
writing. Thank the Lord for this improvement. 
" Your obedient servant." 

This man's idea of having done some great wrong proved to be, 
on careful investigation, a pure delusion. The letter which was 
enclosed would impress one as being merely an expression of 
an over-conscientious individual making of a mole hill a moun- 
tain. Over-conscientiousness and fear of imaginary wrongs 
or imaginary deficiencies occurred in so many of my cases as to 
impress me as being characteristic. One man who had been 
an engineer for a railroad company for over twenty years 
was obsessed with the idea that he had defrauded his com- 
pany and that all of his surveys were erroneous. Finally after 
great mental anguish he went to his employers and confessed to 
faults and errors which he could not be persuaded were not true. 
It was a well-known fact that all his life he was conscientious to 
the last degree and one of the most trusted in the company's 
employ. He soon shifted his anxiety to the fear that his religious 
exj3ressions were not sincere and that he was sailing under false 
colors in holding a prominent position in his church. Soon after 
I was sent for because he said that the health department had sent 
a police officer to arrest him because his house needed fumigation. 
He insisted that his bed and his person were covered with bugs 
and in order to quiet him it was necessary to pretend that a fumi- 
gation was being done. This insane idea was only temporarily 
relieved and reappeared in a few days. 

Another patient, referred to in a previous chapter, told us in 
great distress that she was not lawfully married to her husband 
and that her children were illegitimate. This was the first evi- 
dence of an active insanity and we were not at all suspicious of 
the delusional character of the statement until later in the course 
of her disease it was shown that there was not a vestige of truth 
in it. 

Over-conscientiousness, as before mentioned, a feeling of in- 
sufficiency and lack of confidence, and various religious ideas, 



276 A TREATISE ON PELLAGRA 

especially a fear of the unpardonable sin, delusions of persecution 
and fear, profound melancholia, together with indifference were 
the most common symptoms of mental change in my cases. It is 
impossible for me to fit my cases into the classifications of Gregor 
in every instance, though his classification comes nearer to filling 
the requirements than any other. It will be noted that the case 
of the school teacher who wrote the letter above fits well into 
Gregor's sixth place, that of the anxiety psychoses. To the ques- 
tion: Are there disease pictures of dementia, whose anatomical 
basis is an injury to the brain by the toxins of pellagra? with 
Gregor I would unhesitatingly reply in the affirmative. 

Acute delirium, which is Gregor's fourth group, occurs fre- 
quently in the American cases. Repeatedly it was necessary to 
restrain these patients. Mutism and various flexures of the ex- 
tremities are noted in such cases. They lie doubled up in bed at- 
tempting to conceal themselves beneath the bed clothes. The 
peculiar clonic contractions of the upper extremities are also 
noticed. The outcome in such cases is invariably fatal and the 
condition is the expression of a terminal state. 

Salerio epitomized the mental conditions of his cases thus : 
a frightened state, ideas of persecution or belief that they are pos- 
sessed with the devil ; a suspicious state, the refusal of food and 
medicine ; and an exalted religious state. Suicidal tendencies 
were noted by him. He said that finally they are liable to lapse 
into dementia, paralysis, or tubercular disease. 

Lombroso found that one of the characteristics of the pellagrous 
psychosis was a greater moral impressionability; that a slight 
insult or the threatening of some trivial danger completely pos- 
sesses them. He thought that if pellagrous insanity assumes a 
type it approaches that of chronic mania and dementia more 
closely than monomania. The real or apparent stupidity and the 
obstinate mutism Lombroso called " psychical catalepsy." But 
Babcock, commenting on this expression of Lombroso, says that 
the insanity is of " a misty, ill-defined contradictory character, 
like that produced by old age, or by anemia, and differing in this 
point from general paralysis." 



NERVOUS AND MENTAL CHANGES IN PELLAGRA 277 

Babes and Sion found the psychical symptoms appearing sev- 
eral years after the first appearance of the disease. The first 
symptom noticed was mental weakness. The pellagrous insanity 
was preceded first by spasmodic then tonic cramps and general 
weakness with a final development in a true pellagrous paralysis. 
They state that the cramps of the feet, hands, and calf muscles are 
sometimes so violent as to result in epilepsy, contractions, and 
swooning. They also state that so-called pellagrous epilepsy is 
the result of pain. This is certainly not always the cause, as is 
illustrated in the case of pellagra occurring in a patient suffering 
with tertian and quartan malaria, which was recorded on another 
page. This patient died in a convulsive seizure and had never 
complained of pain at any time during the two years he was under 
observation, nor was there manifested any evidence of pain at the 
time of his death. They mention the so-called pellagrous tetanus 
(Strombio) in which opisthotonus was a symptom. It is stated 
that sometimes the patients are drawn forwards and fall to the 
ground. Choreiform movements were noted and were more fre- 
quent in the head. Eoussel mentioned the important fact that 
delirium does not occur until the spring of the second or third 
year. It is further stated that sadness may advance to mutism 
and refusal of food, but there may be an interruption in the form 
of attacks of weeping or of suicidal or maniacal outbursts. An 
acute attack leaves the patient in a state of exhaustion, depression, 
and hypochondria. With each attack the intellect weakens and 
demeutia gradually develops. 

Babes and Sion conclude thus : 

" Pellagrous melancholia shows various stages : at first, there are 
psychic impediments, followed by apathy or stupor. Delusions of 
sin, of persecution appear. Mania is rare but catalepsy sometimes 
occurs. 

" When paralysis supervenes, euphoria appears, presenting a 
disease-complex like general paralysis, but even in advanced stages 
of the diseases remissions may occur." 



278 A TREATISE ON PELLAGRA 

Antonini gave as his opinion regarding this complex problem 
of the pellagrous psychoses the following: 

" Already in the first stages of pellagra there appears a decided 
modification in the mental faculties ; there is a great impressiona- 
bility, a greater psychical excitability, a slight disappointment 
depresses greatly the tone of feelings, or produces excessive re- 
actions (from the want of initial inhibitory powers). In the 
progress of the disease we can have true amentia, states of mental 
confusion common to all psychoses arising from exhaustion. This 
state can show suddenly an exaggeration of symptoms and lead 
to death with a syndrome of acute delirium (typhoid pellagra) 
and yet it can also present in certain cases a true progressive 
paralysis of pellagra. 

" But a frequent symptom is the obstinate refusal of food, such 
as aggravates painfully the already sad picture of the pellagrin." 

I have noticed that in some of these cases where there was this 
obstinate refusal to take food in any form, that if it was left in 
reach of the patient and the patient was left alone that the food 
would be eaten. 

In a few words Allbutt well states the condition under discus- 
sion. He says : 

" When the patient has thus been the subject of the disease in its 
recurring attacks for three or four years his depression of spirits 
deepens into melancholia of a severe and irremediable kind. He 
commonly suffers from globus. The melancholia may be alto- 
gether dull and heavy, or on the other hand it may have maniacal 
phases: the patient may be moody, self-accusing, and remorseful, 
or he may present maniacal periods, in which misery or a hor- 
rible burning of the skin may drive him to suicide. Systematic 
monomania (' paranoia ') is never seen. As depression may alter- 
nate with mania, so stupor may alternate with the vertigo ; and 
twitchings, tremors, and even epileptiform seizures of the cortical 
variety are not uncommon." 



NERVOUS AND MENTAL CHANGES IN PELLAGRA 279 

In many cases of pellagra are seen symptoms that would justify 
the classification of amentia. The clouded consciousness, inter- 
ference with association memory, hallucinations and delusions, 
anomalous emotional states as apprehensiveness and fear are often 
present in pellagra and are also distinctive of amentia. Paton, 1 
who well describes this condition, says that there is no sharp line 
to be drawn between this condition and acute delirium ; many cases 
can be differentiated only by the longer course in the former. In 
the description of amentia is found reference to a condition in 
which the patient shows signs of restlessness, slight dissociation 
in connected thought, apprehensiveness, and fear of being left 
alone. It is recorded also that he will complain of unpleasant 
thoughts and unpleasant dreams. Disturbance in association 
memory increases and distractibility keeps the attention con- 
stantly wandering, so that when asked a simple question the 
patient begins to reply, forgets the subject in hand and passes to 
something else. All of these symptoms may be noted in pellagra. 
In both conditions hallucinations hold a prominent place. Ideas 
of persecution are noted and the patient suspects the physician 
and attendants in both states. It is said that in amentia the char- 
acter of the hallucinations in the early stages is constantly chang- 
ing. Motor restlessness often associated with extreme talkative- 
ness have been noted in both. Paton says there are two types of 
this disease : " an asthenic type and one in which the confusional 
state is more boisterous and the general motor restlessness greater. 
To the former belongs this confusional or stuporous amentia of 
Meynert; to the latter, the hallucinatory confusion, delirious 
amentia, and the so-called acute hallucinatory paranoia of other 
writers." I am of the opinion that many of the psychoses of pel- 
lagra are true cases of Meynert' s stuporous amentia and that the 
etiological factor is the pellagra poison, whatever that may be, just 
as parturition is a recognized cause of the same condition. 

1 Meynert, " Die acut. hallucin. Formen des Wahnsinns u. ilire Verlauf." 
Allqemein. Ztschr. f. Psych., XXXVIII. Jahrbuch. f. Psych., 1881. Chaslin, 
" La confusion mentale primitive," 1895. Del. Greco, " Sulle varie forme die 
confusione mentale." II Manicomio moderno, 1897 and 1898. See also for 
these references and his views quoted: " Psychiatry," by Stewart Paton. 1905. 



280 A TREATISE ON PELLAGRA 

It must be remembered that certain catatonic symptoms occur 
both in amentia as well as in dementia precox, and these catatonic 
symptoms are not unusual in pellagra. In dementia precox, how- 
ever, these symptoms are much more definite than in the other 
conditions, while in amentia there is greater impairment of con- 
sciousness and more defects in association memory. 

Many cases of pellagra suggest the diagnosis of manic depres- 
sive insanity, and this condition, too, is easily confused with amen- 
tia. Paton says that in genuine cases of mania the flight of ideas 
has certain specific qualities and the interference with conscious- 
ness or with the reception of all forms of sensory impressions is 
less marked. The very fact that in this group of manic depres- 
sive insanity there occur phases of melancholia which later are 
replaced by mania suggest just the condition in pellagra, but it 
must be said that the same alternation of phases also occurs in 
other mental states. During the motor phase of manic depres- 
sive insanity the general restlessness, the psycho-motor activity, 
the lack of coordination of movement with the peculiar jerky and 
impulsive actions, sometimes also tremulousness and unsteadiness 
would not be foreign to the psychosis of pellagra. But the ani- 
mation, the obtrusiveness, the tendency to be meddlesome, and the 
grandiloquence would be very foreign to pellagra. In pellagra 
I have seen maniacal states but they were never of the violent 
type seen in manic depressive insanity. During the stage of de- 
pression in manic depressive insanity occur symptoms which are 
very suggestive of the pellagrous psychosis. The tardiness in 
replying to questions, the emotional depression, the change in 
handwriting due to retardation of voluntary movements, " the con- 
sciousness of subjective difficulties in the association processes," 
vague apprehension which is often increased to marked anxiety 
point strongly to pellagra. 

The psychosis of pellagra does not materially differ from the 
other psychoses in the sense that the whole symptom complex 
must be considered making due allowance for the various phases 
which are constantly changing in so many different states, in ar- 
riving at a diagnosis. 



NERVOUS AND MENTAL CHANGES IN PELLAGRA 281 

A case of pellagra during the inter-eruptive period removed 
from a pellagrous locality might tax the resources of the psychia- 
trist for a while, but the probability is that the record would show 
the diagnosis of amentia of Meynert in the majority of instances. 

The following record is from my case book under date of 
August 6, 1909. The changing phases of her mental state make 
it an interesting case. The difficulties of classification will at 
once be apparent. 

Mrs. L. H., Bladen County, N. C. Age 41 years. Mother of 
five children; the youngest child is fifteen months, the oldest 
fourteen years. No history of miscarriage. She is fairly well 
conditioned. 

Family history has no bearing on present condition. 

She had never been sick until the present trouble began. In 
the spring of 1903, six years ago, she had a painless diarrhea and 
a stomatitis. This recurred every year for six years. In the 
fifth spring she noticed the first signs of an erythema. This year 
the trouble began on May 1 with the following symptoms : stoma- 
titis, diarrhea, marked salivation, globus hysterica, and a very 
disagreeable salty taste. Sometime after this the characteristic 
lesion appeared on the backs of the hands with some desquamation 
which the patient said had existed from the beginning. Physical 
examination of chest and abdomen was negative. She complains 
of " stinging all over " and at the same time says that her flesh is 
dead and numb and the feet and legs burn like fire. Her memory 
is bad and she is very despondent. She sleeps very badly and has 
had only one night's sleep without drugs in a month. Her ap- 
pearance is that of a woman twenty years older than she really 
is and I was amazed when I was told her age. She has signs of 
marked cachexia. Her expression is anxious. Pupils react almost 
imperceptibly to light and imperfectly to accommodation. Station 
is unimpaired. The patellar reflex is diminished. Pulse is weak 
and the rate is 128. Systolic blood pressure is 105. The patient 
says : " When my flesh died I lost control of myself and I now 
breathe through powders and my nostrils are too open and I 



282 A TREATISE ON PELLAGRA 

breathe too freely." She appreciates her mental deterioration. At 
present her mental state is characterized more by hallucinations 
than delusions. Hemoglobin, 85 per cent. Red cells, 4,500,000. 
Whites, 9,400. 

August 15, 1909. The knee jerks are found quite variable, 
differing frequently from the biceps jerks which too are subject 
to marked variations at different times. The patient insists so 
persistently that worms are present in her vagina that an investi- 
gation has had to be made to satisfy her, but she acknowledges that 
she has never seen any of the worms. Of course, none were found. 
She volunteers the opinion that she is crazy. 

August 25, 1909. The language of the patient has become very 
obscene. She is exceedingly restless and cannot be kept in the 
house. Her people are becoming afraid of her. There is still a 
melancholy cast to every mental phase. She has definite delusions 
of persecution and talks of protecting herself. When I remon- 
strated with her about talking so improperly before the children 
and about her calling them improper names I could make no im- 
pression on her or even hold her attention. 

A few days after this she was found with an axe roaming aim- 
lessly about the yard in search for some imaginary person on 
whom she wished to use it. It was not thought prudent to leave 
her at large so she was committed to the State Hospital for the 
Insane where she died in a few weeks. 

The following case is much more characteristic of the mental 
condition of pellagra. 

M. C. Female. White. Unmarried. Age 43. Farming 
class well conditioned. Seen September 29, 1910. 

Family history has no bearing on present condition. She was 
never sick until the spring of 1903, when she says she began to 
decline and in November had typhoid fever. At this time vague 
nervous and mental symptoms of long standing were exaggerated. 
After the fever she regained her full strength and remained well 
until the present year. In May of this year her bowels became 



NERVOUS AND MENTAL CHANGES IN PELLAGRA 283 

affected. This was accompanied by stomatitis without salivation. 
During June it was noticed that her mental state was not normal. 
Her mental symptoms were characterized by over-conscientiousness 
and self-condemnation. She thought that all the trouble in the 
world had been caused by her. She had the fear that someone 
was taking her home away, and besides this particular fear she 
was afraid of everyone and desired to be left alone. She at- 
tempted suicide by jumping into the well. Her complaint was of 
pain in the top of her head. The intestinal disturbance lasted 
several weeks. She was dizzy but never had fallen and she com- 
plained of weakness. She said that she wanted to be helped to 
do right when I questioned her regarding her reason for consulting 
me. There was a history of insomnia of a very obstinate type. 
She imagines the presence of people and hears peculiar sounds. 
She thinks that she is insane and volunteers the information that 
her condition now is the same as after the attack of typhoid. Re- 
plies to questions are inaccurate and given with great tardiness. 
She is careful about her clothing and appearance. 

This patient recovered and has been in good health for over a 
year. All of the mental trouble has disappeared and to all appear- 
ances she is normal. 

The following conclusion of the whole matter by J. W. Babcock 
is worth quoting in full : 

" The association of pellagra with nervous and mental symptoms 
is common. This relationship is that of direct cause and effect, 
and is not an accident or coincidence. 

" Cases of pellagrous insanity have usually suffered from pel- 
lagra with neurasthenic symptoms for some time before the devel- 
opment of mental symptoms. The psychoses are therefore, as a 
rule, the result of a chronic intoxication. 

" Some cases of pellagrous insanity appear to belong to the 
infective exhaustive type of mental diseases, and others rather to 
the toxic group. In view of the fact that these two groups have 



284 A TREATISE ON PELLAGRA 

been embraced under the comprehensive term of confusional in- 
sanity, many cases of the pellagrous psychoses may better be in- 
cluded under the general heading of confusional insanity. 

" It seems to be admitted that the mental condition of pellagrins 
undergoes an early modification. This early mental state may 
be ill-defined or show itself by a greater moral impressionability, 
or greater psychical excitability, or it may be described under 
the general term of neurasthenia. Later inertia appears, the 
patients are apathetic and show psycho-motor impediments. There 
is said to be intellectual hebetude, stupor or even mutism. Thus 
Lombroso's ' psychical catalepsy ' may appear. If they are not 
silent, pellagrins respond with difficulty, or have the air of not 
understanding what is said to them. Insomnia is almost univer- 
sal and depression (psychic pain) is characteristic. Stupor often 
ensues, and confusion, the type of exhaustion and intoxication 
psychoses, dominates the scene. The patients appear frightened, 
become suspicious, refuse food and medicine, are subject to hallu- 
cinations, illusions, delusions, are suicidal (hydromania) and 
have other criminal tendencies. Episodic disorders of memory 
and orientation are observed. 

" The effort is sometimes made to classify the mental condition 
of pellagrins as acute and chronic. The acute commoner symp- 
toms are: Temperature 39° to 41° C. ; neuromuscular excitement, 
subsulti, contractions, muscular rigidity, exaggerated reflexes, 
confusion with phases of exaltation, and marked insomnia. 

" This condition is more common with alcoholism but may be 
engrafted upon the so-called chronic form. It is often manifested 
as an acute collapse-delirium, and is probably the typhoid pellagra 
(pellagra typhosus) of some writers. 

"In chronic cases: Depression, confusion, paresthesias, hallu- 
cinations, and illusions, memory disturbances, insomnia, exag- 
gerated reflexes, ataxia, and terminal dementia. 

" Intermediate forms occur, being marked by alternations of 
depression and exaltation with remissions and apparent recovery. 
Excitement may break forth without cause, especially in the spring 
and summer. 



NERVOUS AND MENTAL CHANGES IN PELLAGRA 285 

" Polyneuritis is sometimes observed. 

" For the chronic form, dementia is the common termination, but 
it may be complicated by paralysis or tuberculosis. 

" In the first attack the pellagra psychosis is an amentia (con- 
fusional insanity). In the latter and progressive phase, marked by 
chronic and incurable cachexia, it is a dementia. It is an inter- 
mittent and progressive amentia, which if not cured, or not early 
fatal, terminates in dementia (Tanzi). Or it may end in chronic 
mental confusion or in pellagrous pseudo-general paralysis (Regis). 

" Depression and confusion are the more common mental symp- 
toms associated with pellagra, but periods of exaltation (excite- 
ment) occur episodically. 

" Strictly there is no mental symptom-complex characteristic 
of pellagra, but pellagra may act as the exciting cause of several 
forms of nervous and mental states, varying from neurasthenia 
to polyneuritis and meningitis, and from simple depression to 
paretic conditions and dementia. 

"Under the influence of the pellagrous intoxication patients 
commit crimes — suicide (hydromania), homicide, infanticide, 
incendiarism, etc. 

" According to the degree or duration of the pellagrous intoxi- 
cation or possibly from idiosyncrasy, the patient is liable to develop 
the symptoms of acute collapse delirium at any time, and die in 
the attack. 

" It is not unlikely that the mental symptoms of pellagra may 
differ by seasons or in different countries and in different parts of 
the same country, just as, broadly speaking, do the physical signs 
and symptoms of the disease. 

" After all, may not Baillarger be right in questioning whether 
pellagrous poisoning does not, like alcohol, produce these various 
neuroses and psychoses according to the reaction of different 
individuals." 1 

1 Babcock, J. W. : " The Psychology of Pellagra." Jour. S. G. Med. Assoc. 
Nov., 1910. 



CHAPTER VII 

DIAGNOSIS 

The diagnosis of pellagra is either very simple or else it is 
attended with great difficulty. When the classical picture is 
found the diagnosis is not difficult even to one who has never 
before seen the disease. With symmetrical erythema of the 
exposed parts of the body, especially of the backs of the hands, 
the back and lateral aspects of the neck, or the face, less fre- 
quently of the feet and lower legs; with a stomatitis sometimes 
attended with salivation; with diarrhea of varying degree; finally 
with symptoms of nervous depression or more serious psychic dis- 
turbance if the disease has existed for a long enough time — when 
all of these symptoms are present there can be no chance of error, 
but it is rather exceptional to find such a case. Many cases whose 
final history would include this entire enumeration are difficult 
to diagnose for the reason that these symptoms do not always occur 
in the regular order which is considered typical. It is no unusual 
thing to learn on taking the history of a case that the patient has 
suffered for from one to five springs with sundry digestive dis- 
turbances including diarrhea, stomatitis, vague gastric disturb- 
ances, and possibly some nervous symptoms before the final out- 
break of the typical erythema which made the diagnosis easy. 
It is this class of cases which presents the great problem of the 
day in pellagra. It is again a consideration of that condition 
known as " pellagra-sine-pellagra," or pellagra without skin mani- 
festation. It has been the policy of this work to exclude such a 
condition, but the fact remains that many of the cases of atypical 
pellagra — atypical in the time of the appearance of the various 
manifestations — die because the diagnosis could not be made 
early enough in the course of the disease to avail anything. One 



DIAGNOSIS 287 

of the previously recorded cases gave a history of five spring at- 
tacks of diarrhea and gastric trouble before the diagnosis was made 
plain by the appearance of the tardy erythema. I have at this time 
a patient under my care who has a diarrhea of several weeks' 
standing which will not respond to any treatment, not even to the 
use of opium, and in whom the first signs of a stomatitis are just 
appearing. Last spring the same thing occurred. There is not a 
trace of erythema, but she is a very old and feeble woman who has 
been indoors during the trying winter months away from any 
action of sunlight. I have ordered her placed in the direct sun 
and hope by this means to prove or disprove the condition as pel- 
lagra. If this patient has pellagra valuable time has been lost 
already, but there were not enough symptoms presented to make 
a diagnosis without an element of unjustified speculation. We are 
told that in the London School of Tropical Medicine the diag- 
nosis is made without awaiting the appearance of skin symptoms. 
In this country at this time we are too inexperienced to undertake 
such a hazardous thing. This is especially so when we remember 
that H. F. Llarris of Georgia has reported the presence of sprue 
in the southern states. It has been said in another place that the 
resemblance of pellagra without skin manifestations to sprue is so 
great that I have never been able to arrive at any means of making 
the differentiation. Allen has shown that in amebic dysentery 
there is another difficulty owing to the presence of a stomatitis in 
this condition as well as the diarrhea. He has also shown that 
amebiasis is a very prevalent finding in North Carolina. 

There is no place in medicine in which a blood reaction of some 
sort would be of so great value. At one time I hoped with Tiz- 
zoni's strepto-bacillus of pellagra to obtain an agglutination re- 
action with the blood serum of a pellagrin. After two years I 
came to the conclusion that this organism was not specific and 
abandoned any further work. Blood cultures from a patient suf- 
fering from a most acute attack or with typhoid pellagra would as 
often as not remain sterile. I decided that Tizzoni's organism 
was probably a non-pathogenic form which entered the blood 
stream through the open wounds of the skin lesion in the acute form 



288 A TREATISE ON PELLAGRA 

which is usually the so-called moist variety, and that the constancy 
with which this organism was found was due to the fact that it 
was one of the inhabitants of the normal skin. This view, how- 
ever, was purely speculative. 

The Noguchi modification of the Wassermann reaction has been 
thoroughly tested in pellagra by Howard Fox, who reported on 
thirty cases so examined. His conclusions were important and are 
here given: 

(1) Cases of pellagra do not often give a positive Wassermann 
reaction. 

(2) A positive reaction, when obtained, is generally weak and 
is easily distinguished from the strong reactions found in syphilis 
and in many cases of leprosy. 

(3) The value of the Wassermann test is not affected by the 
findings in pellagra. 

The value of the Wassermann test while not of direct help in 
the diagnosis is decidedly useful in the differentiation of pellagra 
from syphilis, the disease with which it has been most often con- 
fused. The reader will recall the case of myelitis which we were 
unable to decide clinically as syphilitic or pellagrous, especially as 
the patient attempted to deceive us through his familiarity with 
pellagra. The Noguchi modification was all that was needed to 
show a definite syphilitic condition. For years in the southern 
states pellagra has occurred and many a victim has been done the 
injustice of a death certificate to this effect when there was not 
even the history of an exposure. It was called syphilis because it 
resembled it more than any other disease with which we were fa- 
miliar. The absence of enlarged glands, the general distribution of 
the mouth irritation, the appearance of the skin lesions almost ex-' 
clusively on the exposed portions of the skin surface, the absence of 
a history or the scar of a chancre, the absence of a history of ex- 
posure, the numerous and varied gastro-intestinal symptoms, the 
more or less characteristic nervous manifestations, and the absence 
of the generally distributed skin lesions in syphilis would make a 
differentiation comparatively simple. But it is a well-recognized 
fact to everyone who has studied medicine for any time tliat a 



DIAGNOSIS 289 

patient cannot be trusted to tell the truth regarding syphilis no 
matter what the consequences of a deception may result in, and for 
this reason the Noguchi test is a great help. 

C. C. Bass of New Orleans has reported sixteen cases of pellagra 
in which the complement fixation with lecithin as antigen was 
attempted. Of this number two had syphilis, in one autopsy blood 
was used, and in another there was found in the blood the sestivo- 
autumnal parasites, but exclusive of these cases he found a positive 
reaction in the remaining eight out of twelve. Of this number he 
said that seven were of the mild type and only one was of the severe 
type of acute pellagra. In the four negative cases there was a his- 
tory of severe acute attacks and two were suffering the first attack. 
He found the reaction positive more frequently in the chronic 
mild cases and those showing resistance to the disease which, he 
says, is in keeping with the fact that the complement fixation re- 
action is due to the presence of antibodies for lipoid substances. 1 
" The complement fixation reaction with lipoid substances as an- 
tigen has been found in syphilis especially, in certain cases of ma- 
laria, in a few cases of scarlet fever, and probably in other diseases. 
All these, except possibly scarlet fever, are protozoan diseases. 
The reaction has not been found in bacterial diseases except in rare 
instances." The writer concluded that deductions could not be 
drawn from so few cases and withheld any opinion until further 
work could be done to prove the real value of the procedure in 
pellagra. 

Reference has been made in another place to the finding by the 
British Pellagra Commission headed by L. W. Sambon 2 of a 
peculiar body (see microphotograph, p. 98). The victim was a 
Roumanian girl who had suffered from pellagra for two years. 
These bodies appear to be invariably located in the nuclear ma- 
terial and were found in the cerebro-spinal fluid, in smears from 
the sensorio-motor cortex, and from a blood clot lvine; in contact 
with and posterior to the lower cervical and upper dorsal regions 

1 Bass, C. C, " Complement Fixation in Pellagra." Proc. Nat. Pel. Conf., 
1910. 

2 Jour, of Trop. Med. and Hygiene. London, Dec. 15, 1911. Editorial. 



290 A TREATISE ON PELLAGRA 

of the spinal cord. It will require further study to determine the 
importance of this finding in the diagnosis of pellagra, but it is 
encouraging to know that there is a possibility of some precise 
means of laboratory diagnosis in these questionable cases. 

Recent advance in the study of the etiology of pellagra have had 
a trend in the direction of an animal parasitic cause and many 
analogies have been drawn between pellagra and such diseases as 
trypanosomiasis, kala-azar, and Rocky Mountain fever. This has 
been especially emphasized by the pathologic findings in pellagra 
of perivascular round cell infiltration which is so well depicted in 
trypanosomiasis, and further by the increase in the mononuclear 
elements of the blood which occurs in both diseases. Xo such 
parasite as a trypanosome has ever been found. With the method 
used by Kock for the detection of the trypanosonie in the blood in 
sleeping sickness I have sought for a parasite of like nature in the 
blood of pellagra but to no effect. It is to be hoped that this body 
discovered by Sambon's workers will be proven to have an etiolog- 
ical relation and that we will have some means of determining the 
diagnosis in atypical cases. 

The blood findings in pellagra have theoretically a considerable 
interest to students of the disease. The increase in lymphocytes 
has been regarded as characteristic and significant. In the blood 
report of the Illinois Pellagra Commission 1 we find this refer- 
ence: " With a normal or slightly increased count (to 10,500) the 
small lymphocytes were often increased in percentage (up to 50), 
making a condition of lymphocytosis. Whether this increase of 
lymphocytes, which is absolute and not relative, has any connec- 
tion with the involvement of the mucous membrane of the intestine 
can be only guessed at. It is known that lymphocytes are increased 
in infections involving the intestines in children and sometimes 
in adults. In general debility the lymphocytes have been known 
to be increased. Some such explanation is the probable one in the 
few cases that presented this phenomenon. Polymorphonuclear 
basophiles were present in normal number. In general with a 
count that is approximately normal the differential count is like- 

1 Bulletin of the Illinois State Board of Health. Vol. V, p. 421. 



DIAGNOSIS 291 

wise so." My own experience is that the blood changes are not so 
constant and decided as some writers would have them. In many 
cases other causes may be readily found for the abnormalities. 
I recall one series of cases in which a very definite cause for the 
lymphocytosis could be found other than pellagra. The fact that 
some writers deny the presence of mononuclear increase of the 
blood is sufficient proof of the unreliability of the evidence of any 
blood change. If these changes were as decided as the changes 
found in exophthalmic goitre they would be of great help in the 
differentiation. 

The toxicity of pellagrous blood serum was tested on animals 
by Camurri, 1 Avho attempted to find a maize-precipitine, but he 
found that the toxicity of the blood was inconstant and not to be 
depended on for diagnostic purposes. In the performance of this 
test a small quantity of the suspected serum was added to a stand- 
ard infusion of corn. The mixture was placed at 37° C. for a 
few hours when, if positive, a precipitate is formed. Camurri 
determined that this measure had value only in determining that 
the individual ate corn and that there had been within a short time 
some lesion of the gastro-intestinal tract. This same observer 
stated that he found a constant hypoacidity with increase of 
chlorides in the urine of pellagrins. The combination of these 
two reactions are counted by him important. Marie 2 expresses 
it thus : " He concludes that an individual from a section where 
pellagra is endemic, whose blood shows a positive ' maize-preci pi- 
tine ' reaction, and who for a brief period of time under constant 
diet shows a urinary hypoacidity with increased chlorides, is a 
pellagrin in the initial stage of the malady." It is, of course, 
apparent that these methods are too complicated for general use 
and can be done only by specialty trained laboratory workers. 

Merk 3 thought that the skin lesions of pellagra were always suffi- 
cient for a diagnosis in the absence even of all other symptoms ; 
that the erythema of pellagra was as distinctive as the eruption 

1 Camurri: Lavinder and Babcock's Trans, of Marie's "La Pellagra," p. 278. 

2 Marie, A., " La Pellagra " and Lavinder and Babcock's Trans. 
8 L. Merk, " Die Hauterscheinungen der Pellagra." 



292 



A TREATISE ON PELLAGRA 



of scarlet fever and measles. This would not be a safe rule unless 
the application was restricted to one who was very familiar with 
the variations of the erythematous skin changes. It is not counted 
wise policy to diagnose scarlet fever without the presence of other 
symptoms than the scarlet erythema as there are many causes for 
this class of eruption. My own opinion would be very unsettled 
unless the child presented the characteristic mouth symptoms. 
There are certainly very distinctive symptoms of pellagra to be 
had in the skin. These symptoms have been enumerated at con- 
siderable length in another place. The fact remains that doubt 
often exists in the mind until the patient has been kept under 
observation for some time. I recall the case of a small boy who 
had a symmetrical erythema of the backs of his hands which was 
either sunburn or pellagra. In the absence of any intestinal or 
mouth symptoms it would not be supposed that there could be 
much difficulty. The reader must remember the fact that the order 
of the appearance of symptoms in pellagra is very variable and it 
might have been such a case under observation. The fact remains 
that the physician who is a thoroughly trained pellagrologer was 
in doubt even though the patient, was a well-nourished boy living 
under the very best hygienic surroundings. 

G. F. Gaumer 1 of Yucatan distinguishes pellagra from a condi- 
tion called by him pelagia, which is the result of exposure to the 
weather and the direct rays of the sun. He also distinguishes it 
from pseudo-pellagra. 



Pellagra 


Pseudo-pellagra 


Pelagia 


In the beginning of the 


Normal. 


Normal. 


disease patient com- 






plains of heat in mouth, 






throat, and stomach on 






expiration. 






Sense of taste impaired; 


Normal. 


Normal. 


there is anorexia and 


Sometimes present. 




ptyalism. 







Gaumer, G. F. Trans. Nat. Pel. Cong., 1910. 



DIAGNOSIS 



293 



Pellagra 



Pseudo-pellagra 



Pelagia 



Tongue broad, flabby, and 
irregularly marked by 
red blotches. 

Bowels constipated, fol- 
lowing diarrhea and 
sometimes dysentery. 

Cuticle assumes a scaly 
appearance; scales lus- 
trous, thin, and not de- 
tachable until disease is 
far advanced — seldom 
pigmented; only affects 
the cuticle. 



Pruritus and burning 
deep-seated, aggravated 
by scratching. Affected 
differently by sun and 
shade. 

Muscular weakness 
marked and progres- 
sive. 

Vertigo, occipital head- 
ache, insomnia, neu- 
ralgias and cramps. 

Ocular phenomena gener- 
ally present. 

The gait is usually para- 
lytic, occasionally para- 
lytic spastic, and pro- 
gressively ataxic. 

Mental phenomena pro- 
gressive from slightest 
perturbation to com- 
plete dementia. 

The pellagrin avoids com- 
pany, seeks solitude, is 
melancholic, distrust- 
ful, etc. 



Uniformly red. 



Diarrhea sometimes pres- 
ent. 



Dorsal aspect of all af- 
fected parts become 
erythematous, assumes 
a dark color and are pig- 
mented progressively ; 
scales thick and detach- 
able — epidermis and 
part of trueskin affected. 

Superficial, aggravated by 
sun's rays. 



The same. 



If present can be traced to 
alcohol. 



If present, alcoholic. 



Usual symptoms due to 
alcohol. 



Alcoholic if any. 



Seeks company, avoids 
solitude, confiding, 
cheerful, etc. 



Normal. 



Normal. 



All exposed parts be- 
come erythematous, as- 
sume a dark color and 
covered by large thick 
laminate scales, detach- 
able. Skin either ede- 
matous or hypertro- 
phied. 

Slight, but the burning is 
intensely aggravated by 
sun's rays. 



Normal. 



Normal. 



Normal. 



Normal. 



Normal. 



Normal. 
Indifferent. 



294 



A TREATISE ON PELLAGRA 



Pellagra 


Pseudo-pellagra 


Pelagia 


Epileptiform movements 


Not rhythmic. 


No movements. 


rhythmic and often 






continued to death. 






Pellagra is not limited to 


Limited to alcohol users. 


To persons past middle 


season, age, sex, nor 




life, who have been 


conditions in life. 




much exposed to sun 

rays. 


Attributable to the use of 


To the use of alcohol. 


To those exposed to the 


spoilt corn. 




rays of the sun. 


The pellagrin does not 


Fears death and is gener- 


Indifferent to death. 


fear death, generally 


ally conscious at death. 




unconscious at death. 







Pseudo-pellagra, to my notion, is pellagra. This conclusion is 
based on a study of the recorded cases of pseudo-pellagra and clini- 
cally, at least, I do not see any difference. Xot recognizing maize 
as the etiological factor in the production of pellagra the two con- 
ditions are at once merged into one. 

One of the most troublesome problems that I have had to con- 
front is the differentiation of pellagra and certain weathering con- 
ditions on the hands of elderly men. In such cases it becomes neces- 
sary to rely on the remaining symptoms. It should be remembered 
that many victims of pellagra insist that the skin lesions are 
simply sunburn. I have in mind one of the most typical cases 
of pellagra in my list. The man was a painter; with the first 
exposure on a roof in the spring his hands became badly burned. 
He also had stomatitis, diarrhea, and marked gastric symptoms, 
together with nervous depression. It was impossible to convince 
him that the erythema was any other than the result of his ex- 
posure to the hot sun. In many cases of diarrhea it has become 
a habit to examine the hands for signs of an old erythema or for 
indications of a beginning redness. It is often quite difficult to 
decide whether the atrophic condition of the skin of the backs of 
the hands in elderly people is a result of an outbreak of pellagra 



DIAGNOSIS 



295 



or is due to exposure and hard labor. I have at this time a patient 
with all the symptoms save the erythema, and the examination of 
her hands reveals a condition 
which may be due to a former 
erythema or to the washtub. 

A case with photograph is noted 
(Fig. 30) in order to emphasize 
the importance of the fact that 
all symmetrical skin lesions are 
not pellagra. The child in this 
case presented a very different 
history from that of pellagra; 
there was an absence of stoma- 
titis, diarrhea, and any nervous 
symptom but the presence of a 
persistent rise of temperature. 
The case was carefully studied 
by E. S. Bullock, to whom I am 
indebted for an opportunity to 
see it. There was really no sus- 
picion that the condition was pel- 
lagrous, but the occurrence of 
the lesions on the backs of the 
hands was very interesting. 

Isadore Dyer of ISTew Orleans, 
who has made some of the most 
important observations on pel- 
lagra from the dermatological 
standpoint, emphasizes the im- 
portance of a consideration of 
the whole course of the skin 
process. Referring to one of his 
cases he said: " The photographs are excellent delineations of pel- 
lagra — when you know that they were taken of a pellagrin's hand. 
They would as readily be taken for photographs of a case of blasto- 
mycosis, the papillary character of most of the eruption being quite 




Fig. 30. — Lesion which is not Pel- 
lagra but Occupies Same Loca- 
tion. (Seen through courtesy of Dr. 
E. S. Bullock, Wilmington, N. C.) 



296 A TREATISE ON PELLAGRA 

apparent. Yet the beginning and the course of this eruption on the 
hands was as typical as it could be in a classic case of pellagra." 
After a thorough consideration of the other symptoms, which he 
counted of great importance in the final determination of the disease 
he added : "... It is easily differentiated from vesicular eczema 
by the persistence of the vesicles, the development of papillary 
areas, and by the marginate, erythematous, elevated and infiltrated 
border, all of the latter evidences testifying to a deep-seated affec- 
tion, beginning deep and not a mere catarrhal process started in 
the mucous layer." He showed that each of his cases presented 
types of the disease with points of resemblance to other affections. 
In all the erythema preceded and at one stage there Avas nothing to 
distinguish it from an erythema of the ordinary type and of a 
simple origin. It was shown that as the group of erythema multi- 
forme is studied its variants have been greatly increased, and in- 
cluded with these are many skin diseases of exudative origin due 
to many different causes. He thought it was a mistake to consider 
the erythema of pellagra to be the characteristic symptom especially 
when it had given place to hyperplastic changes in the skin. 

Chronic eczema is the diagnosis under which many cases of 
pellagra in the past in this country have gone. It is not necessary 
to go into a lengthy description of the differences in the skin lesions 
of these two diseases. Suffice it to say that it is only necessary to 
consider the remaining symptoms when there is occasion for doubt. 

One of the most remarkable occurrences in connection with the 
appearance of pellagra in the United States was the confusion with 
the skin condition produced by simple burns. This was noted in 
a report of G. A. Zeller x of the Peoria State Hospital. Speaking 
of the bitter criticism resulting from the universal non-restraint 
policy adopted by his institution he referred to the biennial report 
of 1906 thus : " The rush incident to the rapid growth of the in- 
stitution, when patients were received at the rate of 200 a month, 
was attended by a fatality in the death of Fred Weber, due to 
scalds received while being bathed by an incompetent attendant. 



1 Bulletin of the Illinois State Board of Health, Aug., 1909. George A. 
Zeller, Supt. Peoria State Hospital. 



DIAGNOSIS 297 

The case was promptly placed in the hands of the coroner, as is 
every unnsnal death in this institution, and a searching investi- 
gation ordered. The verdict censured the attendant, but charged 
no criminal neglect." In 1908 there was a repetition of this same 
note in the records of this institution : " The death of George 
Wright, who was scalded on the morning of November 25, was 
directly due to incompetence. He was an untidy and partially 
paralytic epileptic. 

" We maintain two night nurses in our epileptic colony for men, 
and on the morning in question the nurse on duty while bathing 
him preparatory to turning her patients over to the day force in a 
presentable condition, scalded him about the feet. He lived eleven 
days and died from an intercurrent pneumonia, but the coroner 
was called as in every other fatality, and the facts placed before 
him. 

" We give three hundred and fifty thousand baths a year in this 
institution, and the work is performed by expert bathers who are 
retained for that purpose. In the hospitals and infirmaries the 
untidy patients are bathed by the nurses, and this patient passed 
into the hands of an incompetent person who was promptly dis- 
missed." It was stated that the jury was reluctant to accept the 
scalds as the cause of death. This sad occurrence, which resulted 
in the discharge of faithful and innocent attendants, is mentioned 
in the hope that it may be used both as an illustration of the very 
acute character of certain types of the skin manifestations, and 
also to emphasize the importance of a very careful consideration 
of this question of diagnosis. 

Acrodynia or the malady of Paris was first noted between 1828 
and 1830 in Paris and other parts of France and was described by 
Chardon. It is mentioned here for the reason that we have learned 
that there is no such thing as being exempt from any disease. As 
students we were taught that we need not know anything of pel- 
lagra because it did not occur in this country, and in recent years we 
have learned of the occurrence of many other diseases which were 
not supposed to be things about which we would ever have to con- 
cern ourselves. Most cases of acrodynia, according to Stelwagon, 



298 A TREATISE ON PELLAGRA 

occur in the East. There are many points of resemblance to pel- 
lagra and the diagnosis is not always easy. I feel confident that 
in the near future it will be found that this disease is occurring 
in the United States and there is a strong probability that some of 
the cases diagnosed as pellagra are really acrodynia. The ery- 
thema appears on the hands and feet, but is more prone to attack 
the palms and soles than in pellagra. The disease is not so chronic 
nor so fatal as pellagra. In acrodynia there is said to be at first 
marked hyperesthesia of the extremities followed by anesthesia, 
which is not noted in pellagra. It is thought to closely resemble 
ergotism as well as pellagra. 

It is most interesting to note that Sir Patrick Manson saw fit in 
his article on trypanosomiasis to differentiate it from pellagra. 
He said that in pellagra the erythema was characteristic and lacked 
the ringed or fugitive character of trypanosomiasis. It affected 
the exposed portions of the skin chiefly, which was not the rule in 
the latter disease. He further said that pellagra was more chronic 
and instead of lethargy the mental condition is more on the line 
of insanity, and finally in pellagra the seasonal variations were 
distinctive. While for us at this time a consideration of trypano- 
somiasis seems superfluous, there is no way to tell how long before 
the disease will present itself even though we have no knowledge 
of any " fly belts " in this country. The same thing was said of 
the Simulium, but we note that now many competent observers are 
finding this little fly in various sections. The comparison is in- 
teresting chiefly from the standpoint of classification, as many be- 
lieve that it is only a question of a short time before pellagra will 
be classified among diseases of animal parasitic origin and will be 
separated from the group of grain intoxications. 

The most important problem in the diagnosis of pellagra is a 
consideration of the characteristic psychic manifestations in con- 
nection with cases admitted to institutions during the inter-eruptive 
stage. With symmetrical erythema of the exposed portions of the 
body in an individual with a depressive mental state there could 
be no difficulty in arriving at an immediate diagnosis. Unfortu- 
nately cases are often first seen after the fading of an insignificant 



DIAGNOSIS 299 

erythema which has not impressed the caretakers as a matter of 
any importance, and without at least a history of the erythema the 
physician would not be justified in making such a diagnosis. For 
this reason it becomes a matter of the greatest importance to in- 
clude in the taking of the history of all mental cases a careful con- 
sideration of a former symmetrical erythema as well as a history of 
sundry digestive disorders as stomatitis and diarrhea. Marie dif- 
ferentiated pellagra from alcoholism and paralysis in the last 
stages chiefly by an absence of marked disturbances of speech. 
He also noted that the ambitious or melancholy delirium of para- 
lytics is very rare in pellagra. The mental symptoms have 
been mentioned at sufficient length on another page. The reader 
will doubtless be impressed with an absence of any distinctive 
points of differentiation and will conclude that the diagnosis can- 
not be made of pellagra on the psychic manifestations alone. This 
brings up the interesting and important point as to whether the 
pellagrins in our insane institutions are suffering from pellagrous 
insanity or whether the disease has been engrafted on a preexisting 
mental trouble. I notice that the North Carolina Board of Chari- 
ties reported that in the epileptic colony of that state there were 
eighteen cases of pellagra. Was the epileptic manifestations a 
pellagrous manifestation or is it that the mentally deficient are 
more susceptible to the disease just as are alcoholics ? I am of the 
opinion that many of these patients are suffering from pellagrous 
insanity, and on the other hand there seems to be no reasonable 
doubt that the insane of other types are susceptible to the disease. 
It is not an uncommon thing in the southern insane institutions to 
find patients who have been inmates for many years and who sub- 
sequently develop pellagra. 

The reader is to remember the very definite seasonal variation 
in pellagra which will often of itself clear up a difficult diagnosis. 
There are very few exceptions to this rule. While the rays of a 
hot sun are supposed to account for this seasonal appearance it 
should be remembered that there is more than this, that a patient 
confined to a room removed from the sunlight will have an out- 
break in the spring without any relation to an exposure. It must 



300 A TREATISE ON PELLAGRA 

also be kept in mind that the time of the outbreaks will depend on 
the character of the season. In an early season the outbreaks for 
that year will be correspondingly early, while the reverse is also 
true. It is often an aid to determine the month of the out- 
breaks. In pellagra it will be found that the yearly recurrences 
usually occur in the same month year by year, and by this means 
the time of an outbreak can usually be accurately predicted. 

After the subsidence of the attack the patient in the earlier 
attacks at least will regain a fairly normal condition, giving the 
false idea that there has been effected a cure. This is a peculiar 
property of pellagra and should stand out in bold relief in the 
history. 

It should be repeated that in order to avoid errors in the diag- 
nosis the physician must look minutely into the previous medical 
history, for in so doing there is great protection from error which 
otherwise is almost unavoidable. 




CHAPTER VIII 

PROGNOSIS 

From the first writings on the subject down to the present 
it has always been acknowledged that there was 'no such thing 
as a trivial case of pellagra. The earlier writers were dis- 
posed to look on it as an incurable condition that inevitably would 
prove fatal. This view, just as the view of the prognosis of tuber- 
culosis fifty years ago, has undergone many alterations. There 
can be no more difficult phase of pellagra to discuss than the prog- 
nosis because of that remarkable variation of which much has 
been said which this disease manifests. In one section it mani- 
fests certain sectional peculiarities which are not seen in another 
section. The malignity of the cases which gave the American 
medical profession their " baptism of fire " with this disease re- 
calls the outbreak of measles in the Fiji Islands as recorded by 
Osier. In 1875 the disease was imported from Sydney by Her 
Majesty's Ship Dido, and in four months 40,000 out of 150,000 
inhabitants died. Osier gives the mortality of measles as from two 
to three per cent in private practice and in hospitals from six to 
eight or ten per cent. This tremendous death rate of a disease 
which cannot be ordinarily counted as a very deadly one, though 
always serious, is an illustration of a peculiar kind of adaptation 
where the human organism was called on to combat a new and 
strange enemy. The same thing was repeated when pellagra ap- 
peared in epidemic form for the first time in the United States. 
Probably never before in the history of medicine in this country 
has there occurred such an opportunity to study the invasion by 
a new disease of a race never before affected and to see the won- 
derful changes brought about in the nature and course of this 



302 A TREATISE ON PELLAGRA 

disease in a very few years. It is only after five years of observa- 
tion that we see a condition being approached which resembles the 
condition of the disease in its own country. It is readily under- 
stood why the American physician was loath to accept the diag- 
nosis of pellagra, for there were many points in which the Ameri- 
can affection differed from the disease of the Lombardy plains. 
In Italy the disease is always recognized as a very chronic con- 
dition and never acute except as an exacerbation. In the southern 
states we saw enacted in many cases the changes, which usually 
would require a decade in Italy, in so many days or little more. 
It was indeed hard to accept the teaching that this rapidly fatal 
disease was really the chronic condition which so many Italians 
endure in secrecy for many years. 

The first report of an epidemic of pellagra in the United States 
was made by George H. Searcy of Tuscaloosa, Alabama, in the 
Journal of the American Medical Association for July 6, 1907. 
He reported eighty-eight cases occurring in 1906, and of this num- 
ber fifty-seven or sixty-four per cent died. The disease in this 
epidemic ran its course usually in from two to three weeks. The 
acute cases were invariably fatal. In those cases with recovery 
it was very slow and the patient was very feeble for a long time. 

In six cases reported by me 1 in 1909, but which had occurred 
several years before, there were five deaths, and the sixth passed 
from observation after recovering from the first outbreak. The 
first of these died after three attacks ; the second, a child, after 
four attacks in six years ; the third, after the third outbreak ; the 
fourth, after only a few weeks acute course; the fifth, after five 
weeks of an acute course. 

The recording of these acute cases opens up an entirely new 
literature of the disease which, so far, seems to be peculiar to this 
country, for it is not described by the Italians. 

In one house I saw three deaths after an acute course of the 
disease which never lasted longer than six weeks. Two of these 
patients, who were children, died suddenly in bed at night and 

1 Wood, E. J., " The Appearance of Pellagra in the United States." Trans. 
College of Physicians of Phila., 1908, and Jour. Am. Med. Assoc, July 24, 1909. 



PROGNOSIS 303 

were so found the next day. At that time status lymphaticus was 
considered as a cause of death but was not demonstrated. Just 
what the immediate cause of death was we were never able to say, 
but the patients died at the height of the attack and certainly of 
pellagra. Sudden death was not confined to children. I recall 
the death of a prostitute which occurred in 1905, before we be- 
came acquainted with pellagra. She was found dead one morning, 
and owing to her despondency, which was quite marked, the cause 
of death was given as suicide from a drug. 

The prognostic importance of suicide should be remembered. 
Pellagrins often commit suicide even when the attack is compara- 
tively trivial. One of my patients was hauled out of a well where 
she had thrown herself in an effort to suicide. In the American 
cases the percentage of suicides has been much less than in the 
European cases. 

Soon after the appearance of pellagra, in the same town in which 
occurred the cases recorded above, I saw six cases in one house 
without a death. The patients were all under seventeen years of 
age and none of them at any time were confined to bed. In 
spite of poor hygienic surroundings the recoveries were prompt 
and permanent. 

It is possible that our earlier fatality was in part due to our 
ignorance of the real nature of the disease. Since the introduction 
of the arsenic treatment there has been a material decline in the 
mortality. It is hardly probable that this was entirely due to the 
attenuation of the disease, though, of course, it played a part. 
Pellagra is now being treated intelligently and some hope held out 
to the patient. It is no longer regarded as an entirely hopeless and 
incurable affliction. With the earlier diagnosis which a better 
knowledge of the disease will bring there will be even greater re- 
duction in the death rate. 

It cannot be said that the arsenic treatment of pellagra is spe- 
cific, but it can be said with fairness that in no other disease will 
it produce such decidedly beneficial results as in pellagra. 

It should be recognized in the beginning that the very acute or 
fulminating type of pellagra is absolutely incurable and that death 



304 A TREATISE ON PELLAGRA 

is as inevitable as in acute miliary tuberculosis. Fortunately, as 
stated before, this type of disease is rapidly disappearing and in 
a few months, probably, will be a mere matter of history. I have 
not seen such a case in two years or longer. 

It is as important a matter to make an early diagnosis of pellagra 
as it is to recognize tuberculosis in the incipiency. The death rate 
since the subsidence of the fulminating type will depend directly 
on the promptness with which the disease is recognized. Unfor- 
tunately the medical men in many sections have resented the an- 
nouncement of the appearance of the disease in their midst and 
have been loath to diagnose it because, in many instances, they 
recognize in it a disease which has been occurring in their expe- 
rience for years and which they have diagnosed differently. Usu- 
ally this diagnosis has been syphilis. I recall an instance where 
the medical man refused to make the diagnosis or to institute thft 
treatment because the disease lias never been passed on by any 
eminent dermatologist in his particular section. The hard 
pioneer work of his colleagues, which was soon checked up by a 
comparison with the disease in Italy, was discredited. The pa- 
tient died in a few days of typhoid pellagra in the third year of 
the disease. There are still many who will not recognize the pos- 
sibility of the occurrence of this great scourge and, as a result, 
the patient is allowed to go through the first year without treat- 
ment. To attain its highest efficiency treatment must be begun 
during the first year and anticipatory treatment be instituted in 
the early months of the second year before the yearly anniversary 
of the initial outbreak. 

At the present time Lavinder 1 estimates that the death rate in 
the United States is above twenty-five per cent. It has been esti- 
mated that in the asylum cases it has reached sixty-seven per cent. 
It has been pointed out that the estimates in this country are 
largely based on the returns from the insane institutions, hence 
they cannot be considered fair for the reason that insane patients 
are most unfavorable subjects for good results. 

1 " Prevalence of Pellagra," by Babcock and Cutting, W. B., Jr. Senate 
Document, No. 706. 



PROGNOSIS 305 

In the celebrated one hundred cases of the Illinois State Board 
of Health twenty-two per cent of the cases died, ten per cent were 
failing, seventeen per cent were improving, and fifty-one per cent 
recovered. It will be noted on examining this report that in a 
number of these cases there was sufficient cause for death in dis- 
eases exclusive of pellagra. 

In the Alabama insane institutions the following results are 
noted : 

The Bryce Hospital since 1896 

White men 6 

White women 21 

Total ~2T 

Deaths 18 

Mount Vernon (Colored) Hospital since 1896 

Negro men 66 

Negro women 144 

Total "310 

Deaths 121 

Average number of white patients 1,350 

Average number of colored patients 650 

It is interesting to compare the mortality rate of pellagra in 
America with the European returns. 

From Sambon * we learn that in 1899 the census returns showed 
in Italy 72,603 pellagrins with a death rate of 3,836. In 1905 
there were 55,029 pellagrins with a death rate of 2,359. 

Lombroso, according to Lavinder quoted by NTiles, 2 stated that 
in 1883 in 866 Italian civil hospitals 6,025 pellagrins were treated 
with 923 deaths; in 1884 there were treated in 993 hospitals 6,944 
cases with 780 deaths. This mortality then is about 13 per cent. It 
will be noted that in the figures of Sambon above the death rate 
was only little more than 4 per cent. The reader will doubtless 
be impressed with the extreme variability of returns. There are 

1 Sambon, L. W., Progress Report. 

2 Niles, G. M., " Pellagra : An American Problem," p. 174. 



306 



A TREATISE ON PELLAGRA 



many explanations of this great difference in the various reports 
and in the various sections from which the returns have come. 
Reference has been made to sectional variation, and it might be 
added that there is also a certain variation in the severity of the 
outbreaks in different years just as there are differences in the 
malignity of such diseases as influenza in different pandemics. 

The occurrence of certain intercurrent diseases does a great deal 
in shaping the outcome of pellagra. I have already referred to 
a case with a complication in the shape of a coincidental malarial 
infection. Certainly in this case the patient's chances of recovery 
were lessened by this occurrence, if in no other way by a general 
lowering of resistance. In the southern states the prevalence of 
many intestinal infections with various parasites is to be seriously 
considered in arriving at any conclusions regarding the outcome. 
A large number of pellagrins in the South have heavy hookworm 
infection and others have heavy infections with the amebse coli. 
A case has been mentioned in which, the patient passed by anus 
and mouth during the last two weeks of life about one hundred 
round worms. Certainly her resistance was lowered and she was 
less able to stand the pellagra of which she finally died. Tuber- 
culosis acquired during the course of pellagra, which is no un- 
usual thing, or before any symptoms have appeared, materially 
affects the prognosis. I have lost a patient who was doing well so 
far as the pellagra was concerned but who died of chronic inter- 
stitial nephritis. This occurrence is frequently referred to in the 
literature as one of the common events. Acute bronchitis and 
pneumonia often close the scene. Mariani has shown the effects 
of pellagra in the production of arterio-sclerosis. There is little 
doubt but that there is such a relation and it has occurred in 
my experience. It is not improbable that some of our cases of 
sudden death in pellagrins can be attributed to this cause. Alco- 
holism is one of the most potent factors in producing unfavorable 
results in pellagra. This cannot be too strongly emphasized nor is 
there a known fact about pellagra which is so definite and sure as 
this. I have been frequently impressed with the possibility of 
alcohol being a very definite predisposing cause of pellagra, and I 



PROGNOSIS , 307 

have seen death from pellagra where there could be no doubt but 
that the drug took away the chance which the victim had for re- 
covery. There is no phase of pellagra which presents such a grave 
outlook as the complication with alcoholism. 

The prognosis in pellagra is directly affected by the improve- 
ment of general hygienic conditions. A patient removed from un- 
favorable surroundings will be much more benefited than by any 
form of treatment with which I am familiar. I have in mind a 
case which was removed from his home in South Carolina and 
carried to a sanatorium in the North for treatment for pellagra. 
No specific treatment was instituted, but the change and general 
oversight of his diet and habits were sufficient to bring about what 
seems to be a complete restoration which is chiefly indicated in 
great increase in weight and disappearance of all mental symptoms. 

Increase in weight is the best prognostic sign with which I am 
acquainted, and after the subsidence of the usual symptoms of an 
outbreak I rely on the scales in great measure in estimating the 
general condition. This increase is of the same importance and 
significance as increase in tuberculosis. 

Pellagra is always counted a feverless disease and in my expe- 
rience fever never occurs except in case of the coincidental pres- 
ence of a febrile process as malaria. Lavinder states that fever is 
a very grave prognostic sign and in this I would agree, but I would 
also go another step and say that this fever is usually not the fever 
of pellagra but the fever of some such complication as a mixed 
bacterial infection through the raw skin surface occurring in the 
same manner as a like infection in burns. I have never seen fever 
in pellagra which was not attributable to some very definite cause. 
This is well illustrated by temperature charts Nos. 1 and 2. In 
the first the temperature was certainly due to the malarial process ; 
in the second the secondary infection through the raw skin sur- 
face produced by the pellagrous process was sufficient to account 
for the rise, though it is possible that a part, at least, of this fever 
was an irritative process produced by the remarkable infection 
with round worms. Any condition, however, which produces fever 
would be a poor bed-fellow for pellagra and the result would natu- 



308 A TREATISE ON PELLAGRA 

rally be more serious. My explanation for the unfavorable prog- 
nostic importance of fever in pellagra is that, certainly in a large 
number of the cases, the cause is this secondary infection which 
does not occur except when the pellagrous lesion is of the moist 
variety; this would also explain the reason for a larger death 
rate in cases with this condition of the skin. In my experience 
one of the most general prognostic signs of value is the character 
of the skin lesion. The large majority of my cases which were 
fatal were of this class and it was rather exceptional to see a death 
in those cases with dry skin lesions. It must not be taken to mean 
that the prognosis was unfavorable in proportion to the extent of 
the skin involvement. Many of the comparatively mild cases had 
that large involvement of the skin which is known as pellagra 
universalis. 

Allbutt x stated that when a case reached the asylum stage it was 
practically beyond recall and that there were few exceptions to 
this rule: This has not been altogether my experience though 
mental disturbances must be looked on with gravity. Many of 
the cases in my experience which have answered the requirements 
of a cure, that is, have remained well long enough to indicate 
that there was no longer danger of seasonal recurrence, have been 
among that number which manifested all symptoms of insanity. 
With an improvement in the general condition there usually occurs 
a corresponding improvement in the mental and nervous states. 
On the other hand mental symptoms usually indicate that the 
disease has existed for some time and has been making unchecked 
progress in producing definite organic change. It should be re- 
called, however, that one of the cases referred to so often on ac- 
count of the coincidental malarial condition showed definite men- 
tal symptoms before the first pellagrous symptom. Another case 
illustrating this was seen with I. A. Bigger of Bock Hill, South 
Carolina. The patient had been sick for only a few weeks and 
had decided symptoms of a grave mental disorder; one of these 
was mutism and another was a series of motor symptoms. She was 
sent, through necessity, to an institution in the Xorth for the treat- 

1 Allbutt, " System of Medicine," 1905. 



PROGNOSIS 309 

ment of this class of cases. At that time all skin lesions had dis- 
appeared and there was left not a remnant of any of the usual 
pellagrous symptoms so that the physician hesitated about accept- 
ing the diagnosis. The result was a cure. 

One of the most important phases of the question of prognosis 
is a consideration of the bearing of the condition known as " pel- 
lagra-sine-pellagra." All authorities are agreed that an early 
diagnosis is almost essential for a favorable result. An early diag- 
nosis cannot be made in cases of pellagra without skin lesions for 
the reason that these skin symptoms are the pathognomonic sign 
of the disease. My explanation of this atypical form of pellagra 
is that there is an absence of the ordinary sequence of symptoms ; 
that the skin lesions are either very late in appearing, or very 
early before any other symptom, and cleared up before the other 
symptoms appeared, or these lesions were so trivial as to be over- 
looked. Every one will recall the case mentioned by J. J. Watson, 
in which a diagnosis of gastric carcinoma was made, but when 
the patient was wheeled out into the sunshine the characteristic 
erythema promptly appeared. I have at this time a patient with 
a sore mouth and an intractable diarrhea which began as a dysen- 
tery. There is a history of the same condition a year ago, but there 
was then and is now an absence of all skin symptoms though 
sought for diligently. I have had her wheeled out into the di- 
rect sunlight and by this means hope to prove or disprove the 
presence of pellagra. It is a very important matter in her case to 
know whether or not she has the disease, because there are reasons 
why the arsenic treatment should not be used unless actually 
needed. The contraindication chiefly is the presence of a cirrhotic 
kidney. The late appearance of the skin lesions in this case, if it 
be pellagra, will materially influence the outcome. 

Subsultus, tremor, retraction of the head, and sundry motor 
symptoms are counted by many pellagrologers as very unfavorable 
prognostic indications. Such has always been my experience. 
These symptoms seem to indicate a grave intoxication which is not 
usually successfully combated. The most positive indication of the 
approaching end of the patient is that coarse clonic contraction of 



310 A TREATISE ON PELLAGRA 

the muscles of the forearms. I have never seen it except in those 
patients who were in extremis, and I do not recall ever having seen 
it in any case in which recovery afterwards took place. 

Acute exacerbations which are so frequent in pellagra are always 
attended with a degree of danger. When the condition known as 
typhoid pellagra supervenes it is recognized that it is in a way a 
terminal exacerbation and few indeed of the victims ever recover 
from it. It is in this condition that we so often see the clonic con- 
tractions of the muscles of the forearms and other grave motor 
symptoms. 

As in most functional nervous disturbances any operative pro- 
cedure is usually attended with grave risk to the patient. This 
risk consists in the precipitation of an exacerbation. I saw re- 
cently a case of fatal pellagra in a woman who had been operated 
on by H. A. Kelly. The procedure which was necessary was 
immediately followed by an outbreak which was soon fatal. On 
the other hand, the rest cure attending the recovery from an ab- 
dominal section not infrequently acts favorably on the course of 
pellagra. The preponderance of experience is that as a rule any 
surgical procedure is apt to produce an acute exacerbation or to 
light up a latent condition. 

It is to be hoped and rather expected that the National Pellagra 
Conference for 1912 will report that the mortality of pellagra in 
the United States has settled down to the normal percentage which 
obtains in Roumania and parts of Italy. This percentage is said to 
be that of typhoid or about ten per cent. It is very certain that 
when the initial violence has subsided and what might be called 
a normal relation of the disease is established the death rate in 
this country will sink much below that of Roumania or Italy. The 
reason for this sanguine utterance is that the misery and destitution 
which is so common among the peasantry of southern Europe is 
unknown in the United States. Of my certain knowledge there is 
never occasion for a white man or a negro to want in any section 
of the southern states and I presume that the same may be said of 
all sections of the country. The greatest obstacle in the way of 
lowering the death rate from pellagra in the South is the presence 



PROGNOSIS 311 

of hookworm disease, which has done more to retard this section 
than the war between the States. It is a matter of only a short 
time, however, before this great resistance lowering agent will be 
entirely eradicated through the wonderful work of the Rockefeller 
Commission for the Eradication of Hookworm Disease. Already 
throughout the South the poor whites have learned the great bene- 
fits of this work and are eagerly availing themselves of the oppor- 
tunities to cast oif their lethargy and avail themselves of their 
pure Anglo-Saxon inheritance. When this great obstacle is re- 
moved there will be nothing left to hold them back physically, and 
they will be able to cope with the scourge which has so cursed the 
Italian peasantry. 



CHAPTER IX 

PROPHYLAXIS 

A consideration of the question of prophylaxis is approached 
with a great deal of hesitation because of the fact that anything 
that may be said on this subject must of necessity be purely specu- 
lative. Until the question of the etiology is settled no considera- 
tion of prevention could be intelligently discussed. If the attitude 
of this work was to accept the time-honored maize theory, the 
matter would be simple and we would at once consider what bad 
corn is and how to prevent its use. For the sake of completeness 
and from a purely historical standpoint the literature on this sub- 
ject will be reviewed. 

At this time the Simulium theory of Sambon is by far the most 
interesting and to many the most reasonable explanation of the 
etiology of pellagra. If this is finally proven to be a correct view 
of the cause, what measures can be employed to prevent the dis- 
ease ? The Simulium is abundant in many sections of this country 
and from my own investigation I am inclined to think that in 
time it will be shown that this fly occurs in all pellagrous sections. 
In the case of anopheles in malaria and stegomyia in yellow fever 
the problem of infection was easily handled by destroying the 
insect or by screening the patients. The buffalo fly is a field 
pest and its control would be most difficult if not impossible. The 
question would arise when does the fly do the biting which infects 
him; at what stage of the disease can this transmission occur. 
This would be important, because if the fly is the intermediate host 
and cannot be controlled it may become necessary to screen the 
.victim to prevent the further spread, and if this is done it must 
be known for how long a time it will be necessary. On the other 
Jiand, it will be argued that as it is a field pest never entering the 



PROPHYLAXIS 313 

bouse any screening would be superfluous. More must be known 
about tbe life history and babits of this fly as well as more evi- 
dence to incriminate it before we would be justified in any cru- 
sade against an insect that may be harmless. 

My colleague, R. H. Bellamy, is at present engaged in a study 
of a possible relationship between, the bedbug and pellagra. He 
is working on the theory that this insect is an intermediate host. 
It has been frequently noted by him as well as by many others 
that this pest is often found in great numbers in the houses of 
pellagrins, but this does not argue that wherever there are bedbugs 
there will be pellagra. 

Mizell's * theory is that pellagra is caused by the consumption 
of semi-drying oils taken as food. Among these oils he empha- 
sizes cotton-seed oil and takes the stand that this oil, as well as 
pork fattened on cotton-seed hulls, causes pellagra by some pecu- 
liar metabolic process. The recent expression of Zeller's in this 
connection should be remembered. He said that it was bad policy 
to condemn a good food on such paltry grounds. I shall always 
make it a point to use these oils whenever the patient's digestion 
will bear them in the same way in which I would attempt to im- 
prove the nutrition in tuberculosis. In my opinion cotton-seed 
oil is a very nutritious food and a splendid substitute for lard. 
It is certain that this product played no part in the pellagra of 
the time of Casal and Strombio and by the same sign the matter 
may be dismissed here. 

Bayard Cutting, Jr., United States vice-consul at Milan, in 
writing of the corn theory made this expression : 

" The doctrine is, in the present state of science, insusceptible 
of direct proof and of direct disproof. It cannot be disproved for 
two reasons : first, because it is impossible to show that any given 
patient whose food was corn ate only healthy corn, whereas it is 
easy to demonstrate the presence in spoilt, of a toxic substance. 
If the corn was well matured, it may have been badly kept, or if 

1 For a consideration of this subject see the Journal-Record of Medicine. 
Atlanta, Vol. XVII, Nos. 5 and 12. 



314 A TREATISE ON PELLAGRA 

well kept it may have become spoilt after being ground into flour. 
The flour may have been sound, but have been cooked so badly as 
to allow decay in the polenta or corn bread. There is always a 
chance that a man who has eaten corn at all may have eaten spoilt 
corn. The second reason why the Lombrosian theory is hard to 
disprove is that cases of pellagrous patients who have never eaten 
corn are hard to find, and when they are found they can be dis- 
missed as examples of some other disease. The symptoms of pel- 
lagra are so varied, even in Italy, that they impinge frequently 
on those of other maladies. Every province, according to Lom- 
broso, has its own peculiarities; a fortiori, we must add, every 
country. This variety of symptoms allows much latitude to the 
theorist; in perfect good faith he is able to include as examples 
of pellagra such cases as suit his preconceived ideas and to reject 
such as have a contrary tendency. 

" Pure zeism, as has been said, is no more capable of direct 
proof than of direct disproof. Experiments with the poison of 
spoilt corn have indeed induced serious, and even fatal, results on 
all kinds of animals, and on some human beings ; but they have 
not induced the precise disease, pellagra. Nor has it been conclu- 
sively shown that the poison enters into the human system ready 
made, and not in the form of a bacterium. And there are no es- 
tablished quantitative relations between the amount of poison 
absorbed and the progress of the disease. Professor Ceresoli, for 
instance, experimented on himself for two months, eating every 
day a large dish of polenta made of the most moldy corn he could 
find. At the end of two months he had noticed no evil symptoms 
of any kind. The poison had failed to operate. Why ? Probably 
because in addition to bad polenta, he had eaten good food of other 
kinds. There must also be a predisposing cause or a debilitating 
disease, such as typhoid fever, tuberculosis, syphilis, frequent 
child-bearing, poverty, insanity, or other condition producing ex- 
haustion or lessened powers of resistance. Pellagra appears most 
easily (if not exclusively) among those whose diet is corn, good 
or bad ; or at least among those who live mainly on corn and other 
vegetable foods ; and among such persons it is probable that a very 



PROPHYLAXIS 315 

small amount of pellagrozeina, as Lombroso calls the corn poison, 
is sufficient to induce the disease. 

" Accordingly, among the anti-zeists we meet first with those 
who call pellagra the disease, not of corn, but of poverty. The 
corn explanation appears to them not so much false as inadequate. 
It is true, perhaps, that little or no pellagra is found in places 
where corn is unknown ; but such a concession to zeism appears 
to them purely formal. Look at the places where pellagra is found. 
In Spain, where it takes several forms, it appears in districts 
where corn is either not cultivated or constitutes only a small part 
of the peasant's diet. In France, the inhabitants of the Landes 
used to eat corn, but other grains as well, and in far larger quan- 
tities. Even in Italy some of the largest corn-growing districts 
have the least pellagra, or none at all. If in answer to this the 
Lombrosian says that the districts in question are exempt pre- 
cisely because their corn is good and does not become moldy, 
their opponents can point to regions where the crop is exception- 
ally fine, yet pellagra abundant; and to others, near by, where 
the corn is bad, and pellagra scarce. No kind of statistical curve 
can be drawn with corn statistics which has any definite corre- 
spondence with the pellagra curve — whether the area of culti- 
vation, the amount of the crop, or its market price be taken as a 
basis. And then the anti-zeists point to huge corn-fed populations 
like those of Mexico, Poland, and — till to-day — the United 
States, where pellagra is entirely unknown. They do not deny 
that in Italy corn is a cause of pellagra ; but the cause they find in 
the inadequate nutrition and poverty of the peasant, who is en- 
feebled during the long winter months by an inadequate vegetable 
diet, and whose debility takes a violent and specific form when 
the labor of the spring begins. 

" The poverty theory is almost too indefinite to criticize ; it is 
itself little more than a criticism." He says further : " To tell 
a peasant not to eat corn is about as practical as to tell him to be 
rich, but to prevent him from eating a certain diseased part of 
the corn, and to advise him to harvest and store it in a certain 
manner, in order that it may not become diseased, does not exceed 
the bounds of possibility." 



316 A TREATISE ON PELLAGRA 

In Italy the problem of preventing the people from eating dis- 
eased corn is one which holds an important place in the affairs 
of the nation. It is considered there to be a problem entirely of 
prophylaxis rather than of cure. The whole attention is directed 
toward the improvement of living conditions among the rural and 
agricultural population. It is counted most important to exclude 
moldy corn and its products from the diet of these people. The 
Italians further claim that no good remedy has been found except 
a radical change of food. The crusade along this dietetic line was 
begun by Joseph II of Austria who gave all his influence and aid 
towards the measures for the control of this great scourge. The 
hospital founded by him was the one in which Gaetano Stronibio, 
the elder, made his fame. Cutting further said : 

" The first serious attempt, in Italy, to deal with pellagra, was in 
1879, ten years after Lombroso's famous essays. A census was taken 
of the pellagrous patients in Italy, and as a result of the census a 
bill was introduced for the regulation of corn cultivation and im- 
portation, and the establishment of public desiccating machines. 
The bill failed and the only immediate result of the census was 
an annual grant of 36,000 lire ($5,790) from the government 
toward the relief of pellagra — about six cents for each patient. 
This amount was raised at a later date until it amounted to 
70,000 lire ($13,510) in 1899; and under the law of 1902 
100,000 lire are contributed annually for the prevention and cure 
of pellagra, and as much more for the introduction of improved 
methods of agriculture. The census of 1879 was an epoch-making 
event. It brought home to the people as a whole the gravity of 
the situation, and it stimulated the various provincial governments 
to act independently. Many provinces appointed pellagrological 
commissions, took censuses, and founded hospitals, or locande 
sanitarie. From 1879 to 1903 was a period of local and provin- 
cial activity. The conclusions of doctors were tested on a small 
scale, and the way prepared for general legislation. Meanwhile, 
in 1895, the Crispi administration had issued an ordinance for- 
bidding the importation of spoilt corn, and providing for inspec- 



PROPHYLAXIS 317 

tion at the chief ports. In 1902 the ' Law for the Prevention and 
Cure of Pellagra ' was passed, and in the following year was is- 
sued the regulations for the enforcement of the law. Since that 
time four years have elapsed, and already pellagra may be said 
to be a doomed disease. The statistics, so hard to interpret as 
regard particular details, bear unmistakable testimony to a gen- 
eral decline in the disease under the operation of the law. 

" The main provisions of the law are as follows : 

" (1) Absolute prohibition of the importation, sale, holding for 
sale, or grinding of spoiled corn or products of corn destined for 
human food. If the corn is destined to feed animals or to be 
used for other purposes, it is admitted only by special permit of 
the prefect. 

" (2) Obligation upon all communes to report cases of pellagra. 
A commune with several cases is declared pellagrous, and falls 
under the following provisions: 

" I. Government inspection of all corn dried, stored, and con- 
sumed in the commune. 

" II. Obligation on the part of commune and province to es 
tablish public desiccating plants, to provide curative nourishment 
for all patients, to provide patients and their families with free 
salt, and to treat severe cases in special institutions. 

" III. Establishment of pellagrological commissions in all prov- 
inces affected with the disease. 

" IV. Assignment of a government grant of 200,000 lire an- 
nually and obligation upon provinces and communes to defray, 
in equal portions, the expenses entailed by the act." 

He says further, commenting on these provisions: 

" This is the charter under which the struggle against pellagra 
is now being carried on. It proposes to examine the several dispo- 
sitions of the act; then to give some details in regard to certain 
provinces which the writer has been able to investigate in person, 
and finally to append such statistical data as will give an idea 
of present conditions in Italy as a whole. 



318 A TREATISE ON PELLAGRA 

" The dispositions of the act are of two kinds, curative and 
preventive. The curative measures, which may be examined first, 
fall into several classes, distribution of salt, administration of 
food, either at the patient's home or at sanitary stations (locande 
sanitarie), treatment of severe cases in hospitals, pellagrous hos- 
pitals (pellagrosari) and insane asylums. The prophylactic mea- 
sures are most numerous. Those to be chiefly noted are: The 
testing of corn and flour brought in at the frontier or offered for 
sale or brought to the mill, the exchange of bad corn for good, 
desiccating plants, cheap cooperative kitchens, the improvement 
of agricultural methods, and the instruction of the people as to 
the danger of bad corn." 

A plentiful supply of salt is thought by the Italian govern- 
ment to have a tendency to counteract the bad effects of a corn 
diet. Seventeen and a half pounds for an adult and eleven poimds 
for a child is the yearly allowance of the government. 

According to Cutting, the amount of salt distributed gratui- 
tously from 1904 to 1907 is as follows: 

1904-5 1,953,469 lbs. 

1905-6 2,520,553 lbs. 

1906-7 3,118,628 lbs. 

The law of 1902 makes a curative diet for the indigent victims 
of the disease obligatory on the part of the government. Two 
periods of at least forty days per annum in which this prescribed 
diet was required was the specification of the provincial pella- 
grological commission. The distribution is made from house to 
house, by the use of economic kitchens, and by sanitary stations. 

In certain provinces where the disease is thought to be under 
control the distribution is made to families through the cemmnnal 
authorities. ~No special instruction is thought necessary in such 
cases. 

The economic kitchens supply sound food to the rural popu- 
lation at small cost. These kitchens are the property of the com- 
munes and sometimes of charitable organizations. Sometimes these 



PROPHYLAXIS 319 

kitchens are made use of to supply the free food when there is 
no locanda or sanitary station near by. Cutting says that in 1906 
there were one hundred and seventy-one of these kitchens in Italy, 
and in 1907 the number had grown to one hundred and eighty- 
seven. 

The sanitary stations (locande sanitarie) are an improvement 
on the cheap kitchen. The first station was established in Bergamo 
in 1884. To these stations the pellagrous patients come once or 
twice a day and receive suitable food, which they eat on the spot. 
This food consists of soup, bread, meat, and wine, with a certain 
amount of cheese and vegetables. It is hoped by this means to 
build up the underfed pellagrin and thereby increase his resistance. 
The time selected for this treatment is the spring and autumn 
when the outbreaks of pellagra are expected. 

While the locanda has been the subject of criticism, it is claimed 
that they accomplish a great good in retarding the progress of ad- 
vanced cases and effecting a cure in many incipient cases. It 
is claimed that eighty per cent of the patients go away distinctly 
improved. The usefulness seems to be in direct proportion to the 
length of time the institution is run each year. It is further 
claimed that the provinces which have been most successful in 
controlling pellagra are those well supplied with these locanda. 
The provinces of Bergamo and Brescia are examples of the good 
accomplished by an abundance of locanda. run a sufficiently long 
period. 

There are twenty-two special hospitals or pellagrosari in Italy 
for the care of the pellagrous. These institutions care for the cases 
too far advanced for the dispensary plan of treatment. The plan 
adopted by them is described as dietary, balneary, and medicinal. 
The dietary plan is about the same as in the locanda. The medici- 
nal treatment embraces numerous baths, as sulphurous, ferrugi- 
nous, arsenical, and saline. These hospitals are supported by the 
government and by private subscription. Some of these insti- 
tutions, as the one at Inzago which was visited by Cutting, limit 
their cases to a certain period of life and to a certain stage of the 
disease, because their mission, even in this class of institutions, 



320 A TREATISE ON PELLAGRA 

is understood to mean prevention, and it is hoped to effect this 
by taking the young (in this case between twelve and twenty years) 
and preparing them for life. It is probable in the natural course 
of events that in this country at no very distant time it will become 
necessary to make some such provision as this for the care of our 
own cases. When that time comes it is to be hoped that this ex- 
perience of Mr. Cutting will be held in mind. He said about 
this institution at Inzago: 

" The effort of Director Cav. Giuseppe Friz is to secure the chil- 
dren of pellagrous patients, and to take them into the hospital the 
moment the first signs of pellagra appear. The statistics of the 
hospital are admirably kept. Every detail in regard to a patient's 
past history, to his family, to the diet to which he is accustomed, 
and to his precise symptoms, are carefully registered at the time 
of his admission. His weight is then taken and his strength 
tested. During his stay a record is kept of his diet, of the medici- 
nal cure administered, and of the results upon his system. Finally 
a systematic effort is made to record his history after leaving the 
hospital." 

It is more and more the policy of the Italians to remove from 
the villages the pellagrous insane to the insane institutions where 
special treatment is provided. It is a well-recognized fact that 
Italy is second to no other country in the character of their care 
of the insane, as well as their skill as psychiatrists. 

Cutting says that the provisions of the laws of 1902 and 1903 
are adequate to protect the people from bad corn brought from 
abroad. The suspected cargoes are examined by experts and when 
the corn is condemned it is sent to the distillery or else is dena- 
tured. The tests for spoilt corn have been mentioned on another 
page. It is said that such indications as mildew or the odor of 
mold are sufficient proof of its unwholesomeness, but it is further 
emphasized that these may be corrected by drying in the sun, so 
that their absence is of no importance. 

" But the peasant should be warned against any corn that is cov- 



PROPHYLAXIS 321 

ered with dust, that is, damp to the touch, or that gives forth any 
smell of mold when warmed in the palm of the hand. He should 
he on his guard against corn of a pale color with a dull surface." 
( Cutting. ) 

It has been pointed out that the inspection of corn on the 
frontiers is comparatively easy, but at the mills or in the mar- 
kets, especially when in the form of meal, makes a much more 
difficult problem. The government ownership of grist mills would 
be necessary in order to control the adulteration of meal, thinks 
Cutting. This plan is strongly advocated by the Italian pella- 
grologers. 

Cattedre ambulanti are institutions of an educational char- 
acter in Italy which disseminate exact knowledge of agriculture 
to the farmers. They cooperate with the health authorities in 
encouraging the farmer to abandon the objectionable forms of 
maize. For example, the much-dreaded quarantino is shown to 
be a poor crop, and a form of maize which requires a longer time 
for maturity is advocated. This objectionable grain is being 
abandoned in many sections. The peasant is taught to plant the 
Mathilde potato in place of both quarantino and cinquantino. 
Cutting found many evidences of the presence of an excess of 
pellagra in those provinces where quarantino is still generally 
grown. 

The artificial drying of maize is a new departure in Italy. 
It has largely supplanted the more primitive methods of hanging 
the ears of maize on the rafters or drying frames in the houses 
of the peasants. In some instances the grain was dried in the 
open air. The fault lay in storing the corn in poorly ventilated, 
dirty places. Cutting says : 

" If Italy is the home of pellagra, while Mexico and Burgundy 
are entirely free from the scourge, the difference may be due simply 
to the fact that in Mexico and Burgundy corn is fired almost as 
soon as harvested. Artificial desiccation is the most important of 
all prophylactic measures against pellagra. It has objections, how- 
ever, to encounter from the peasantry. The corn loses weight, 



322 A TREATISE ON PELLAGRA 

they say. This is true ; but the weight lost from decay is greater. 
It will not germinate. This is true likewise, if the desiccation is 
not properly performed; but the best desiccators leave the corn 
with all its natural properties unimpaired. It is expensive. Not 
so expensive, on the whole, as the outdoor frames. The 
best desiccator yet contrived, that of Pietro Cattaneo, dries 
110 pounds of corn with a fuel consumption of 1 per cent. 
Nevertheless, in order to remove, as far as possible, the objec- 
tion of expense, the law of 1902 provides that every family 
may dry at the public desiccator, free of charge, so much corn 
as is required for the household needs. Further use of the desic- 
cator must be paid for, but at rates which allow nothing for 
profit. 

" Desiccators are of two types, — fixed and portable. The port- 
able type has the great advantage of saving the cost of transpor- 
tation of the corn. It can be carried in sections and set up in 
the middle of the corn belt. It is cheap enough to be within the 
means of peasants. The fixed type, however, is infinitely prefer- 
able. The air is kept at an even temperature and circulates 
equally in all parts of the machine; thus none of the corn is 
spoiled or deprived of any of its properties. A pamphlet describ- 
ing the Cattaneo desiccator is enclosed. Air heated by a furnace 
is forced by a ventilator into a chamber of seven stories. Each 
story is a circular revolving wire tray, containing about 1,390 
pounds of corn. The top tray is filled from above. After a cer- 
tain time its contents are emptied by pressing a lever into the 
tray below in such a way that they are thoroughly remixed. The 
corn thus passes gradually to the bottom tray, whence it goes to 
a receptacle, where it is cooled by means of a ventilator, and 
thence out of the machine by an incline plane. The first tray 
load of corn takes seven hours to pass through the machine ; after 
that 1,400 pounds come out each hour. The cost of the machine 
is about $540 and the power required to run it about 2 1 /o horse 
power. Larger machines of the same kind, costing about $1,840, 
have a daily capacity of 88,000 pounds and require an engine of 
S horse power. In the Cattaneo desiccator the air is forced through 



PROPHYLAXIS 323 

the trays in both an upward and a downward direction; the air 
which absorbed dampness from the corn is replaced constantly by 
dry air; the temperature is kept low (about 104° F.) with 
economy of fuel and without risk of injuring the corn; and the 
mechanism is so simple that the machine can be handled by any 
laborer of ordinary intelligence." 

The use of the public desiccator for moldy corn is avoided 
because a temperature sufficient to be effective under such 
conditions would burn up the grain. In 1904 there were 179 
public desiccators; in 1905, 221; in 1906, 389, and in 1907, 
461. In 1907 there was desiccated 54,747,000 pounds of 
corn. 

The law of 1902, about which much has been said, gave the 
power to the commune to establish public storehouses for the 
grain of the peasantry who could not supply suitable accommo- 
dation for their maize. Owing to the cost this has not yet been 
accomplished, but the advantage is immediately appreciated. The 
storing of the grain in the dark, ill-ventilated huts of the peasantry 
could be nothing but unhygienic, and a prevention of this evil is 
devoutly desired. 

The establishment of rural bakeries has done much to do away 
with the use of maize as a food in northern Italy, and the substi- 
tution of wheat and other foods in its place. It is predicted that 
it will not be long before maize will cease to be an article of diet 
in Italy altogether. 

Ceresoli introduced the plan of exchanging good maize for the 
inferior qualities of the peasant, giving in return a smaller amount 
of good grain. While this plan was found not to be very ex- 
pensive and to meet the approval of the pellagrologers, it has not 
been successful. 

None of these measures could be objected to, even by the most 
pronounced antizeist. It is evident that maize, owing to its large 
amount of fat and its very poorly protected embryo, as well as its 
water content, is very subject to deterioration and is therefore 
easily rendered unwholesome, to say the least. Any measure look- 



324 A TREATISE ON PELLAGRA 

ing to a protection of the grain from any form of decomposition 
must appeal to the mind without regard to any consideration of 
the possible relationship to pellagra. It has been shown that 
in this country bad corn is to be found on the market, and we 
know that some has already been condemned by government offi- 
cials. As before stated, the question of water transportation can 
be passed over, as practically no corn is shipped in this way in 
this country. The shipping of corn from the western states to 
the southern states should be considered. It is not infrequent 
that a carload of corn is refused by the local dealer because of the 
" heating " process which has occurred in transit. This detection 
seems to require no skill. What becomes of this " heated corn " ? 
It is supposed to be sold for such purposes as the feeding of poul- 
try, but it is questionable if this is always the use to which it 
is put. There should, of course, be a more rigid supervision of 
this corn, as well as a more rigid inspection of all com. It is 
hardly probable that the trouble in the United States is with the 
quality of corn raised. If there has been any change it would 
seem that such a change would be for the improvement of the 
grain. Certainly the farmer has been well instructed lately re- 
garding the growth of what has been called " the great American 
cereal." 

Alsberg, 1 after considering the methods of cultivation of corn 
in this country and finding nothing there to account for pellagra, 
then considers the fact that in the last eight or more years the 
climatic conditions have somewhat changed. He shows that we 
have had a preponderance of cold wet falls and late springs. 
He emphasizes the importance of the Indian summer to produce 
the best grade of corn. As this weather has been lacking in late 
yearSj the corn has been harvested in an unripe condition. He 
thinks that the outbreak of pellagra at this time is a most sig- 
nificant , coincidence. He shows that there is a tendency for the 
extension of the corn belt farther to the north and the west be- 
cause the wheat lands of the northwest are not so productive as 

1 Alsberg, C. L., " Agricultural Aspects of the Pellagra Problem in the 
United States." N. Y. Med, Jour., July 10, 1909. 



PROPHYLAXIS 325 

they were. It is possible that the limits of safe corn cultivation 
have been exceeded. 

It is said that more corn has been harvested in this country 
before it was entirely ripe than formerly. Owing to this extension 
northward and also to the changing season corn is not thoroughly 
hardened and dried before the harvest, according to Alsberg. 
The moisture content of corn being greater than of any other 
grain, it is all the more difficult to prevent molding. It is shown 
that even ripe corn imperfectly dried is subject to mold. This 
imperfectly dried corn, possibly unripe, does not spoil during cold 
weather, but with the coming of the warm season. 

Alsberg says: 

" Corn is transported in closed cars without ventilation. The 
grain of corn is a live thing. It is breathing, consuming oxygen, 
giving off carbonic acid, and as the result of its respiration, heat. 
The heat thus given off increases the rate of respiration till the 
corn heats up hot enough to create ideal conditions of tempera- 
ture and moisture for the growth of fungi. Corn transported thus 
into the northeast may have its tendency to ferment checked by 
the colder climate. Corn shipped to the South will on the con- 
trary have the tendency to ferment augmented often by the warm 
moist climate. Quite in conformity with this fact, is the ex- 
perience of the United States Department of Agriculture with 
shiploads of corn exported from the seaports of the two sections 
to foreign lands. Shipments from the north Atlantic ports are 
not so apt to become spoiled ; as we go South more difficulty is 
experienced; while the greatest difficulty is often encountered 
with shipments from Gulf ports. . . . The remedy then is to 
cause the corn to be thoroughly dried before transportation. To 
bring this about, corn must be sold on a basis of its moisture con- 
tent. But to make this possible there must be an efficient impartial 
system of grain standardization. Such a system under the com- 
plex conditions of our present civilization can, without doubt, be 
best carried out by the Federal Government. Federal grain stand- 
ardization would hot merely tend to restore to us our lost markets, 



326 A TREATISE ON PELLAGRA 

it would not merely increase our economic efficiency, it would 
not merely make for higher business morals and greater com- 
mercial honesty, but it would also be a most important public 
health measure. Such legislation would be as truly a potent 
influence in our public health as a Federal quarantine." 



CHAPTER X 

TREATMENT 

Until we have a solution of the question of the etiology 
of pellagra the consideration of treatment must be, in a 
measure at least, unsatisfactory. In the United States there 
is a growing dissatisfaction regarding the accepted theory 
of the etiology. There are many, and the number seems to be 
steadily increasing, who will not accept the damaged maize theory. 
This same condition of things is found in England. It is signifi- 
cant that at the meeting of the London Society of Tropical Medi- 
cine and Hygiene in December, 1911, the work being done by 
Sambon and his followers was endorsed, and it was officially 
announced that the society rejected the maize theory. 1 Could we 
accept the maize theory this chapter would resolve itself into a 
consideration of an improvement in grain conditions. As this 
theory cannot be accepted and as the evidence in favor of Sambon's 
hypothesis grows day by day, we must look at the all-important 
question of treatment from all standpoints. 

Certainly there can be no consideration in medicine in this 
country at this time of any greater importance. Last year E. H. 
Martin 2 estimated that there were 100,000 cases of pellagra in the 
United States and predicted half a million for the year 1912. 
Such figures call for the gravest consideration, and as at this time 
our efforts along the line of prophylaxis are pitifully wanting in 
effectiveness, it behooves the whole profession to give greater 
heed to the question of treatment in the hope that some specific 

1 Jour. Soc. Trop. Med. and Hygiene, Dec. 11, 1911. 

2 Martin, E. H., "The Arylarsonates in the Treatment of Pellagra." Read 
before 27th Annual Session Tristate Med. Soc. ( Miss., Ark., and Tenn. ) , Nov., 
1910. 



328 A TREATISE ON PELLAGRA 

may be found. It is encouraging to recall that a specific was 
used for syphilis many years before a determination of the 
etiology. 

The drugs which have been tried in the treatment of pellagra 
are countless. It is a notable fact, however, that only those reme- 
dies containing arsenic in some. form have stood the test of time. 
Coletti and Perugini were the first to employ this drug in the 
treatment of pellagra, and this treatment was revived and given 
new impetus by Lombroso, who also claimed that the same benefits 
could be derived from the use of sodium chloride. This latter 
drug was found to be badly borne by the stomach and conse- 
quently never became popular, except in so far that provision was 
made by the Italian government to provide salt for the sufferers. 
Salt is a government monopoly in Italy and the price is often too 
high for the purse of the poor peasant. During the years 1006 
and 1007 the Italian government distributed 3,000,000 pounds 
of salt. 

Among the drugs prominently advocated is quinine by Isadore 
Dyer * of New Orleans. His justification for this treatment is 
thus expressed: 

" For years I have treated all types of toxic erythemas where the 
specific cause was not determined with quinine and salicylic acid 
salts. The success arrived at made me give quinine in the first 
case, and I have continued to use this as the mainstay in each 
case of pellagra that I have had to treat, or for which I have 
advised treatment. In each case the symptoms were promptly 
controlled with quinine (given usually as the hydrobromate) in 
good-sized doses and by keeping up the quinine continuously. 
In two cases the symptoms have disappeared entirely. In two 
last cases the treatment has not been followed long enough to 
establish a definite report, but each case has improved enough 
to make the prognosis favorable. I have no argument to make for 
quinine, as I have used it with empyric judgment and have con- 
tinued its use because the results have been good — so far." 

1 Trans. Nat. Pel. Cong., 1910. 



TREATMENT 329 

I have obtained no results from quinine, except in those cases with 
a coincident malaria. As pellagra and malaria occur in the same 
parts of the country, it is no unusual thing to find a complication 
of malaria, and in such cases, of course, quinine influences the 
course of the illness favorably. 

W. S. Thayer gave one case thyroid gland with good result, 
but this experience has not been repeated, as far as can be deter- 
mined by the literature. 

It is important at the outset of a consideration of this subject 
to decide just what the criterion of a cure shall be. Many writers 
have claimed great things for sundry therapeutic measures when 
their observations were based on one year's experience. Any 
remedy will be likely to be accounted a specific under such a 
test, for the disease process will subside in the course of a few 
weeks, in the majority of early outbreaks, under any form of 
treatment. It cannot be said that pellagra is a self-limiting disease, 
for it will recur year after year unless curative measures are 
adopted, but it can be said the pellagra outbreak will subside 
without treatment unless the attack is sufficiently severe to cause 
death. As a rule the disease does not come under observation 
until the outbreak is well advanced and often not until near the 
end. If the inexperienced observer applies a remedy in such 
cases and, because the patient recovers from the attack, assumes 
that the drug was the cause of the recovery, he has fallen into an 
error which will be proven by a recurrence during the following 
spring. This source of error accounts, in a large measure, for the 
large number of drugs which from time to time have been vaunted 
as specifics. A patient who has been under treatment for pellagra 
should not be counted recovered until two years have elapsed 
without any recurrence. It is unknown in my experience to see 
a case which has passed two years suffer a recurrence, but it is 
no rare thing to see a patient escape one attack and have a re- 
currence the next year. This two-year rule is as important as 
the five-year rule for the recurrence of carcinoma. It is impor- 
tant also, having this rule in mind, to keep pellagrins under treat- 
ment as long as leutics. It is only fair that these people should be 



330 A TREATISE ON PELLAGRA 

told that their disease will require three years of treatment and 
to enjoin on them their responsibility in cooperating with the 
physician. Many cases have recurred in my experience because 
the patient failed to obey the instructions regarding the time of 
returning for the anticipatory treatment. After all symptoms 
of an outbreak have well subsided it is my custom to abandon 
the arsenic treatment until a time which is one month ear- 
lier than the month in which the original outbreak occurred. 
For example, as the month of March is often the time of the 
outbreak in my section I have my patients come early in Feb- 
ruary and receive one month of vigorous treatment — just as 
vigorous as the treatment of the outbreak. If this rule is strictly 
adhered to the recurrences in the majority of cases will be 
prevented. 

As the idea of the protozoal origin of pellagra has grown in 
favor, the use of arsenic has been more generally resorted to in 
the hope that it would have the effect that it was found to have 
in trypanosomiasis. One of the main arguments in favor of an 
animal parasitic origin of pellagra was that these arsenic deriva- 
tives had such a decidedly favorable effect. Since the introduction 
of this form of treatment the whole aspect of the medical pro- 
fession towards this dread disease has undergone a tremendous 
change. In the United States the first cases of pellagra were of 
the fulminating type and none recovered, in spite of treatment 
with atoxyl and soamin. It has been said that the prognosis in 
this class of cases was as unfavorable as the prognosis in acute 
miliary tuberculosis, and an analogy may be drawn between these 
two diseases in regard to treatment. It has been proven that 
tuberculosis is one of the most amenable diseases to treatment, 
provided it is recognized early enough. Just so with pellagra, 
when the ordinary type is detected early and active treatment 
instituted, there is no reason why the prognosis should not be 
as favorable as the prognosis of tuberculosis under the same con- 
ditions. Certainly such has been my experience, with the ex- 
ception that in children pellagra is a comparatively trivial disease, 
as a rule. 



TREATMENT 331 

Babes 1 in Roumania was the first to suggest the use of atoxyl 
in the treatment of pellagra. But the drug at that time was by 
no means new. It is a difficult matter to find anything about atoxyl 
in English medical literature, so at this point it will be mentioned 
at some length, taking it as a type of the arylarsonates. My own 
experience has been limited exclusively to the use of atoxyl, as 
it has been entirely satisfactory, but I am now instituting the 
use of soamin in my hospital cases on the strength of the favorable 
experience of Babcock of South Carolina and E. H. Martin 2 of 
Hot Springs. The only reason for this trial of soamin is that it 
is said to be less toxic. 

Georgopulos 3 says that Bertheim found atoxyl to be the para- 
midophenylarsenate of sodium, containing 24.1 per cent of arsenic 
and not the metarsenanalid (C 6 H 5 XHAs0 3 ), containing 37.69 
per cent. It was found to have an elective action on the blood, 
the skin, the nervous system. Thomas of Liverpool was the first 
to use it in diseases of protozoal origin. It was employed experi- 
mentally in the treatment of the trypanosome of surra, nagana, 
and sleeping sickness, using for the experimentation rats, mice, 
and rabbits. The results of Mesnil and Nicolle were not very 
encouraging. The healing action of atoxyl in trypanosomiasis 
was first demonstrated by Robert Koch in a large number of cases. 
Uhlenhuth, Gross, and Bickel found atoxyl not only a healing, 
but also a preventive agent in experimentally produced Dourine- 
krankheit, whose cause is a trypanosome. The great importance of 
the study of atoxyl consists in acquaintance with the varied mani- 
festations of toxicity. The dose of the drug was supposed to be 
about one-third of a grain before its use in pellagra, but to-day it 
is being given hypodermically in as much as seven and a half 
grains (0.5 grams). This dose has been known to produce such 
symptoms as chills, fainting, headache, blindness from retro- 

1 Babes, A., " Tratumental Pelagerei cu boluri de carna cruda." Spitalul, 
Bucuresci, 1901, XXI. 

2 " The Specific Treatment of Pellagra," by E. H. Martin. Read before Med. 
Soc. of Southwest, October, 1911. 

3 Georgopulos, " Die Behandlung der Malaria mit Atoxyl." Munch. Med. 
Wochr., March, 1908. 



332 A TREATISE ON PELLAGRA 

bulbar neuritis, colic, loss of appetite, insomnia, albuminuria and 
the presence of casts in the urine, red and white blood cells in the 
urine, vomiting, dryness of the throat, retention of urine, fever, and 
cough. Often symptoms of a profound intoxication are mani- 
fested in vomiting, pain in the stomach, nephritis, and retinal 
hemorrhage. It was found by Blumenthal 1 on the rabbit that 
thirty hours after the administration of atoxyl arsenic could be 
recovered from the urine. The greatest amount of arsenic was 
found in the blood in from two to four hours after administration. 
This same writer, in spite of the warning of the danger which 
sometimes attends its use, began the treatment of malaria with 
seven and a half grains (0.5 grams), given by hypodermic every 
clay for three days ; then the same amount every other day, and 
finally with three days between the doses. In this way the patient 
received in eighteen days sixty-seven and a half grains (4.5 
grams), which is more than we usually give in one season to 
the severe cases of pellagra. Many evidences of the danger of 
the drug, especially in regard to the eyes, are to be found in 
the literature, and these will be mentioned at some length. It 
is only fair to say that I have never seen any untoward effects 
from the use of atoxyl except in one case, where the symptoms 
of acute arsenical poisoning were produced, but later this same 
patient was given the maximum dosage repeatedly without any 
repetition of these symptoms, which has led me to suspect that in 
the first instance the hypodermic injection was prepared with 
very hot water and we are taught that hot water will decompose 
the drug. It must be prepared with the strictest attention to 
asepsis, but without any heat. It has been shown by W. Jakimow 
that light does more to decompose the solution of atoxyl than does 
a high degree of heat. For this reason the hypodermic tablets 
which were for a while prepared for the American trade were a 
great aid in avoiding decomposition. It is unfortunate that the 
manufacturers have seen fit to withdraw this product of one-grain 
tablets from the market. At this time the only tablets on the 
market are the one-third grain, the use of which when the close 

1 Munch, Med, Wochr., 1907. 



TREATMENT 333 

is from six to seven and a half grains, is absurd. An effort is 
now being made to have the solution dispensed in ampoules con- 
taining six grains or possibly a little more, using a dark colored 
glass. Unless this is done it would be preferable to abandon the 
use of this drug and substitute soamin. It should be an unvarying 
rule either to give atoxyl in large doses or not at all. It is, there- 
fore, all the more necessary to watch the patient with great care. 
It is never wise to give this treatment unless the attending phy- 
sician is competent to make ophthalmoscopic examinations, and it 
is far better to have the patient where this can be done by a skilled 
oculist. Even in blindness from the use of atoxyl the eye changes 
are difficult to find in many cases, therefore the most skillful and 
painstaking examinations are indicated. Of course with the first 
eye symptom the treatment should be abandoned. It is also neces- 
sary to watch the urine, for the reason that the drug has been 
found at times to produce very decided kidney irritation, which 
may amount to a permanent change. It is my custom to have a 
competent oculist watch the eyes in my cases of pellagra, but he 
has never had occasion to call a halt in the treatment. I have 
used the drug in a large number of cases and have reports of 
equally as many cases among my medical friends throughout 
North Carolina and never yet have we had any untoward 
results, though they have been expected and looked for. It is 
possible that our favorable experience has been due to the fact 
that the drug is very carefully prepared for use without heat and 
that the intervals between treatment are made; longer than the 
European plan. We usually give from five to seven grains every 
fourth day in the beginning and later increase the length of the 
interval. The results have been so gratifying that the disease 
is no longer dreaded as in the beginning of our experience. In 
North Carolina atoxyl has been very largely employed and the 
results are almost invariably favorable. When first used the 
dosage was too small to produce any favorable effect and hence 
the unfavorable reports at that time ; then, too, the disease was 
of the fulminating type which would not respond to any form of 
treatment. ■ • - - . 



334 A TREATISE ON PELLAGRA 

Koch 1 found that in sleeping sickness atoxyl produced splendid 
results, but he reported twenty-two cases of blindness, which was 
one and a half per cent of the cases observed. The ophthalmo- 
scope did not show any changes and the optic nerve was not 
affected, as far as could be determined. Xonne objected to the 
name of atoxyl, because it was a very toxic substance, producing 
blindness in six of his cases. He said that it produced a descend- 
ing neuritis. In one of his autopsies was found a parenchyma- 
tous degeneration of the fibers of the optic nerve. Igersheimer 2 
did some important experimental work on the effects of atoxyl 
on the eye of the rabbit and also the effects of the use of the drug 
hypodermically in dogs and cats. Injections into the anterior 
chamber produced no pathologic changes. The injection of one 
milligram into the crystalline lens produced severe macroscopic 
and microscopic changes. The direct contact produced a necrotic 
effect on the nervous elements of the retina. In the dog very 
few general symptoms were produced, but in the cat a very inter- 
esting group of symptoms resulted. Among these symptoms were 
slowness of movement, ataxia, spasms, spastic parapareses, and 
in the eyes there often appeared conjunctivitis as well as other 
optic nerve and retinal changes. 

Babes in Roumania was the first to use atoxyl in the treatment 
of pellagra. Later Babes, Veseliu, and Georghus 3 treated a 
series of cases by the hypodermic injection of 0.5 grams of atoxyl, 
employing at the same time an inunction of five grams of a one-to- 
fifty preparation of arsenic trioxide in lanolin, and by the mouth 
administration of three-fiftieths of a grain of arsenic trioxide in 
one day. This treatment was repeated at varying intervals, de- 
pending on the individual needs of the case. The results were 
most gratifying, and there were no untoward effects. I recall a 
case in which this treatment was used "without modification. The 
case was considered hopeless, but two years have elapsed and the 

1 Koch, " Schadliche Folgen der Atoxylbehandlung." Deutsche Med. Wochr., 
1907, No. 46. 

2 Igersheimer, " Exper. Stud, ueber die Wirkung des Atoxyl." Munch. Med. 
Wochr., 22 Sept., 1908. 

3 Babes, Veseliu, and Georghus, Berlin, Jclin. Wochr., Jan. 8, 1908. 



TREATMENT 335 

man is at his usual labor. He lost only one week from his work, 
as all of his symptoms which were at the height at the time of 
treatment rapidly subsided. It is not usual that such heroic 
treatment is necessary. Usually from five to seven and a half 
grains (0.35 to 0.5 grams) is a sufficiently large dose. At the 
beginning of the treatment the interval between doses is four 
days, but this is gradually lengthened as improvement becomes 
established. The drug should never be administered by the 
mouth, as it is decomposed by the acid gastric juice. 

It was a notable fact that the end results of atoxyl treatment 
were often delayed. It was no uncommon thing to send out of 
the hospital as unimproved and incurable cases of pellagra which 
subsequently, without any further treatment, made good recov- 
eries. The histories and later course of these cases would indicate 
that this treatment was not merely of benefit temporarily, but 
also permanently. The following case illustrates the usual results 
obtained by this treatment. 

C. P. White. Age, 60. Came under observation in July, 1910. 
He was emaciated and his weight was 95 pounds, though his usual 
weight was about 160. He was a painter, but for three years 
had been forced to abandon his work. In addition to weakness 
and emaciation he was suffering from a profuse diarrhea, having 
from twelve to twenty movements daily, and also a catarrhal 
stomatitis with some salivation. On the backs of his hands there 
was found the typical erythema of the moist variety with a num- 
ber of large blebs. He was melancholy and at times emotional. 
All reflexes were increased. 

On every fourth day he was given hypodermically 0.33 grams 
(5 grains) of atoxyl and on intervening days an ampoule of the 
arsenite of iron, which represented one-seventieth of a grain of 
arsenic trioxide. This was administered in the same manner 
as the atoxyl. For months his diet had been greatly re- 
stricted and when these notes were made he was eating only 
soda biscuits and milk. After two weeks of treatment his symp- 
toms were greatly improved, and in six weeks all symptoms ex- 



336 A TREATISE ON PELLAGRA 

cept weakness, which was much less, had been relieved and he was 
on a diet composed of rare beef, potatoes, wheat bread, and milk. 
His improvement was rapid from this time. At intervals for 
four months the treatment was discontinued. He was instructed 
to return in March for more treatment, as his previous outbreak 
had occurred in April and it seemed advisable to anticipate, if 
possible, the likelihood of a recurrence. Although the patient 
failed to report at this time as requested, he escaped with only a 
slight erythema of the hands and with no further symptoms of 
pellagra. Two years later he died of chronic interstitial nephritis 
under my care. 

It is an important fact that in those cases treated with atoxyl 
there will appear about the anniversary of the original attack a 
slight erythema, which usually amounts to a simple redness and 
is accompanied by none of the constitutional symptoms of the 
disease. At the second anniversary this erythema is absent, as 
a rule, though recurrences will sometimes occur on the first and 
second anniversaries without other symptoms. The cause of these 
outbreaks without other symptoms cannot be found, but it can 
be said that this condition should not be counted as a true re- 
currence nor is it of any great significance. It does not indicate 
any unfavorable state of the patient. 

In another place there is a reference to a female patient who 
received the atoxyl treatment and, though her symptoms were 
grave with decided mental deterioration, she has made splendid 
progress. It is a year since the beginning of her affection and 
she has just had the usual outbreak of erythema without other 
symptoms. In November when treatment was begun she was in 
a pitiable condition. The erythema and diarrhea had subsided, 
but the mental state was very distressing. Her weight was about 
one hundred pounds. Since that time the improvement has been 
rapid, and in April she has gained twenty pounds and all the 
depressive mental symptoms have disappeared. There is no doubt 
but that she will make eventually a good recovery. The success 
of the atoxyl treatment in this case was largely due to the co- 



TREATMENT 337 

operation of the patient. In such cases as this we are almost 
forced to accept atoxyl as a specific, and in many cases, as men- 
tioned, it seems to have almost as great specific effect as mercury 
in syphilis. Such results are most encouraging and the observer 
is forced to admit that there is certainly a degree of specificity 
in this treatment. Could the drug be administered in a way 
that would remove the toxicity, no better remedy could be asked 
for and our discussion would stop at this point. It is to be hoped 
that some of the untoward results are due to faulty technique. 
It is known that the atoxyl of the French differs in degree of 
toxicity from that of the Germans, therefore may we not hope 
that there are possibilities of the discovery of other errors and 
variations, the correction of which would give us a safe product \ 

The fact that the returns from the use of the arylarsonates 
are often very tardy should be held constantly in mind. Many 
cases pass from our observation and the clinical record is marked 
unimproved, but many of these patients subsequently make good 
recoveries. Reference has been made to such a case. Treatment 
should not be abandoned because returns are not immediately 
forthcoming. 

Soamin is the trade name for another arylarsonate, which is 
closely allied chemically to atoxyl. The only difference is said 
to be in the water of crystallization, but according to E. H. Martin 
there is five per cent more arsenic in soamin than in atoxyl. 
There seems to be decided differences regarding the relative 
arsenic values of these preparations. Lavinder and Babcock 1 state 
that the percentage of arsenic in soamin is twenty-two and in atoxyl 
twenty-six. Martin considers soamin as an amino-phenyl-arsonate. 
In more exact terms it is sodium-para-aminophenylarsonate, 
having the structural formula NH 2 C 6 H 4 ,ASO(OH)ONa,5H 2 0. 
This drug has been much used by Babcock, one of the most ex- 
perienced pellagrologers in the country, and his employment fol- 
lowed a disappointing experience with atoxyl. I have not had 
occasion to use it up until this time because atoxyl has always 
accorded such satisfactory returns since I learned how to ad- 

1 Lavinder and Babcock's translation of " La Pellagra," by A. Marie. 



338 A TREATISE ON PELLAGRA 

minister it and the proper dosage. In the light of Babcock's 
experience and the favorable report of E. H. Martin of Hot 
Springs, Arkansas, as well as the difficulty of securing atoxyl in 
a satisfactory form I have begun the use of soamin, but my results 
cannot be recorded at this time so that the reference to this drug 
will be gleaned from the splendid report of Martin. It seems 
quite probable that soamin is much less toxic than atoxyl. The 
usual dose of soamin is ten grains, which represents two and a 
quarter grains of metallic arsenic and is equal to four grains 
of arsenic trioxide and more than one-half ounce of Fowler's 
solution, but still no arsenical symptoms are produced by this 
administration. When given in over dose there will be produced 
gastric pain but no diarrhea, insomnia, nervousness, dizziness, 
ataxic gait, a cloudiness of vision, amblyopia, and sometimes optic 
nerve atrophy. Martin emphasizes the fact that this is not arsenic 
poisoning and that the arylarsonates are new drugs in toto and 
not merely preparations of arsenic. He says further that it is 
a question if arsenic is a specific in syphilis, but states as a fact 
that these preparations certainly are. This observer has used 
atoxyl extensively, but abandoned it for the less toxic arylarsonates 
and finally decided that soamin was the safest. In the beginning 
of his experience with this drug he used it in much larger dose 
than now thought necessary, but he has never seen a case of 
amblyopia as a result. He mentions a case in which the patient 
took the drug without advice after he had given a course of sixty- 
five grains. The patient added one hundred grains in ten in- 
jections so that he received two hundred and sixty-five grains 
without an interval. One hundred grains is counted the maxi- 
mum amount for a course and this should be followed by a pause 
of three weeks, hence it was not surprising that this excessive treat- 
ment was followed by optic nerve atrophy. The sight, however, 
was gradually restored and at the end of six months vision was 
perfect in one eye and greatly improved in the other. Martin had 
heard of two other cases in which complete amaurosis was ascribed 
to the use of soamin, but it was learned that partial atrophy pre- 
ceded the use of the drug;. He has reduced the dose from ten ajains 






TREATMENT 339 

to five grains on alternate days, and as a consequence has had no 
bad results ; but he is careful to have eye examinations when there 
is the slightest occasion for it. He had under his care eight cases 
of pronounced pellagra and five suspected cases. The five sus- 
pected cases were promptly relieved of the suggestive symptoms 
by a few injections of soamin. Of the eight pronounced cases only 
five could be treated; the others were too far advanced. The five 
made apparent recoveries in a few weeks, but only one case has 
been kept under observation for more than a year. He employs 
the anticipatory treatment, which has been found by me to be 
of such great benefit in the use of atoxyl. The following interest- 
ing report of a case treated with soamin speaks well for that 
remedy : 

" The patient was Mrs. J. M. K. of J^ewton, Alabama, aged 39, 
white, 6-para, family history good. Had been an inveterate eater 
of corn bread and still longed for it. Had had indigestion for 
several years, but no previous diarrhea. She came under my 
care on July 10, 1910. Four or five months previously she had 
become listless and moody, and ceased to take interest in anything. 
Three months before I saw her the eruption appeared on her hands 
and diarrhea began. She became progressively worse, and when 
I took the case both arms were in bloody bandages, being denuded 
from above the elbows to the finger tips. There was a lesion in 
the right axilla, which had probably been superinduced by trauma, 
as there was no corresponding lesion in the left axilla, and pella- 
grous lesions are practically always symmetrical. She had also 
lesions on both feet and around the anus and vulva. The most 
remarkable ones were on her face, one covering the entire fore- 
head and another merging into it, covering nose and cheeks and 
surrounding her nose and mouth. 

" She was having on an average ten bowel movements every 
twenty-four hours. The right pupil was slightly larger, but both 
reacted to light. Patellar reflexes were normal in the right leg, 
absent or nearly so in the left. She was rational during the day, 
but said that she did not feel so when left alone, and she was 



340 A TREATISE ON PELLAGRA 

delirious every night and could not sleep much. Her tempera- 
ture ranged from normal to 100° F., but her pulse was usually 
120. The tongue and mouth had the usual boiled red appear- 
ance, and nourishment had to be forced. She was weak to pros- 
tration, and had been way-billed by several physicians to her 
home and a speedy death; in fact, her father was with difficulty 
persuaded to allow her to remain a few days to see the result 
of the first injections, and had she not been really too weak to 
be moved she would in all probability have been taken on home 
to die. 

" But five days later, after having received three injections of 
soamin, amounting in all to eight grains, all opposition was 
waived. An improvement could be noticed in her skin, and the 
bowel movements were only six or eight per diem. 

" After the fifth injection, amounting in all to fourteen grains, 
her improvement was marked, skin lesions were drying and not 
seeping as before, and bandages could be left off. Bowel move- 
ments five per diem. 

" August 1, three weeks after beginning treatment, had had 
nine injections, amounting to twenty-one grains. There was new 
epidermis forming on all lesions, some spots entirely covered, 
bowel movements three per diem. 

"August 11, thirty-two days after beginning of treatment, she 
was able to go home; had had twelve injections, amounting to 
twenty-seven grains. All lesions were covered with new epidermis 
and the face was clean. The bowel movements were two daily. 
She called at my office and weighed seventy-six pounds; ten 
pounds of this had probably been gained during the month's treat- 
ment. Her husband guessed her weight at sixty pounds when 
treatment was begun. Her average weight when well was one 
hundred and twenty pounds. 

" On September 19, letter stated that the injections of soamin 
were being continued, two grains every fourth day. She was 
doing some hand work and could walk a mile without trouble, 
although the pains in her feet from the old neuritis bothered her 
greatly. 



TREATMENT 341 

" October 6, a letter states that improvement continues, but 
still has pains in feet and head ; weighs eighty-five pounds. 

" November 7, letter states that patient weighs ninety pounds 
and eats everything except corn bread, which is not permitted. 
Digestion good. Can do light housework. Her finger nails have 
loosened at the roots and are renewing. She still gets the in- 
jections, and has now had about sixty-five grains in four months. 
The treatment will be stopped at one hundred grains, and if it is 
renewed next spring there is no reason to believe that she will 
have a relapse." 

This patient at Christmas was still in good health and weighed 
one hundred and three pounds. This case is a fair illustration 
of what can be done in pellagra if the treatment is persisted in 
for a long enough time, using caution about the dosage, always 
having in mind that the ideal treatment consists in giving the 
largest possible dose without producing toxic symptoms. 

When salvarsan appeared it was eagerly sought as a safer and 
more effective drug in the treatment of pellagra. In my own 
experience the results have been most discouraging, and I much 
prefer atoxyl. My cases did not even show temporary relief. 
Yesterday one of my patients who was given the salvarsan treat- 
ment last summer returned with a fresh outbreak. He said that it 
required several weeks for him to recover from the effects of the 
treatment last summer. His outbreak this spring was no less 
severe than formerly. In my opinion he would have been much 
better off if he had been given the atoxyl. Why salvarsan is not 
effective I do not know. It may be that in this form of treat- 
ment the arsenic effect is not kept up long enough and the amount 
of arsenic is not so great as in a course of soamin or atoxyl. My 
colleagues tell me that their experience, too, has been unsatis- 
factory. Crowell and King have used salvarsan in nineteen cases 
of pellagra with favorable results in the majority of cases. It is 
generally accepted that the drug does no good except in those 
cases with a coincident syphilitic condition. 

E. H. Martin summarizes thus: 



342 A TREATISE OX PELLAGRA 

(1) Soamin will relieve all of the symptoms of most cases of 
pellagra ; it fails only when the condition of the patient is so 
feeble, complications so severe or the disease so aggressive that it 
cannot be given in sufficiently large doses. Usually it causes no 
reaction unless given in over five-grain doses. Some cases would 
require more and could not stand the reaction from the endo- 
toxins. Given in ordinary doses, it must be kept up for several 
years, the time yet uncertain. It is probable that if ten-grain 
doses were safe that there would be no relapse, at least so one 
physician reports to me. 

(2) Salvarsan causes no symptoms if properly given to healthy 
people. In short, no disease germ, no reaction. 

(3) The fever following the administration of salvarsan to a 
case of syphilis is not due to the drug, but to the endotoxins released 
from the killed germs; and is both diagnostic and prognostic. 

(4) The fever following the administration of salvarsan to a 
case of pellagra is not due to the drug, but to the endotoxins re- 
leased from the killed germs ; and is also diagnostic and prog- 
nostic, and further proves beyond a doubt that pellagra is a para- 
sitic disease caused by a micro-organism vulnerable to " GOG." 

(5) That it is at least reasonable to believe that this organism 
is a spirochete or a spirillum. 

(G) That the character of the reaction, the duration, of the 
fever especially, shows that the germs of pellagra are located 
principally in the brain and spinal cord. 

(7) The endotoxins released by the destruction of the pellagra 
germs are so highly toxic to the human host that the dose of the 
drug must be proportioned in order not to destroy too many micro- 
organisms at one time, or the results may be disastrous to the 
patient. Observing patients given large doses of salvarsan, one 
can readily believe that in some cases a condition paralleling the 
so-called " congestive chill " in malaria might be produced. 

(8) Salvarsan does not cure pellagra in one dose, owing to 
the invulnerability of the germs at an early stage of development. 

(9) Prompt disappearance of symptoms shows that the older 
germs are killed. 



TREATMENT 343 

(10) That small and increasing doses, repeated within the time 
required for the development of the germs from the invulnerable 
stage to just before the stage of reproduction, gives us a rational 
treatment of pellagra and should offer as much certainty of a 
cure as quinine in malaria when properly given with respect to the 
seventh day. 

While these conclusions of Martin are based on a speculation, 
they are at least suggestive and interesting. The outcome of the 
present work on etiology which is being pushed in so many quar- 
ters will be awaited with added interest by those who share this 
view. 

Favorable results have come from the employment of sodium 
cacoadylate in the treatment of pellagra. In those cases where 
atoxyl and soamin cannot be administered because of idiosyncrasy 
or otherwise it should be considered. When given it should be 
used in the same dosage as in syphilis, that is, three grains. One 
strong point in favor of the employment of this drug is the very 
convenient ampoule in which it is dispensed. I have seen splen- 
did results from the use of this preparation. Its use has not been 
general enough to make a very definite report. 

Arsacetin was employed by Ehrlich as a substitute for atoxyl 
and soamin. It is the acetyl of atoxyl and is found on the market 
in the form of a salt. 

The solution of the arsenite of iron which is known abroad as 
Zambeletti's solution has been effective in my hands. It is es- 
pecially well suited for combination with one of the above-men- 
tioned arsenic preparations. It has been very successfully used on 
the days intervening between the atoxyl and soamin administra- 
tions. As it is administered hypodermically, the objection of 
Lombroso to the use of iron because it was not well borne by 
the stomach in pellagra is done away with and a much-needed 
preparation of iron is found which cannot be harmful. As a 
rule there is no anemia of any consequence in pellagra, but it 
will be recalled that a large percentage of pellagrins are infected 
with hookworm and consequently are in need of iron ; in such 



344 A TREATISE ON PELLAGRA 

cases this preparation is well adapted. The amount of arsenic is 
comparatively trifling and adds nothing to the value of the prepa- 
ration. Of course this preparation is not indicated except when 
anemia is present. It will be found that it is a satisfaction to the 
patients to have some treatment every day, and this drug fills this 
bill well. Usually when the victim applies for treatment he is de- 
pressed and thinks that the treatment should be formidable in pro- 
portion to the gravity of the disease. Deception is not necessary, 
but it is necessary to make him sufficiently well contented that he 
will remain under treatment for a sufficiently long time. These 
patients, especially when they come from a distance and are not 
confined to bed, are prone to become dissatisfied because of the 
three or four days between treatments. It is a common occurrence 
for the patient to leave after one or two treatments, in spite of 
the fact that he may be beyond the reach at home of a physician 
who could administer the drug. It is quite a problem to be able 
to prevent this occurrence. 

Fowler's solution and Donovan's solution have been employed 
in the treatment of pellagra from the first suggestion of the value 
of arsenic in this disease. There can be no doubt of their efficacy 
in mild cases where an immediate arsenic impression is not im- 
portant, but time is too often lost in waiting for the effect. The 
importance of early treatment cannot be too often nor too much 
emphasized. For the reason of this tardy action and the fact 
that both these preparations are too toxic to be given in doses 
large enough to produce the desired result I consider them a 
menace to the successful treatment of pellagra. An exception 
should be made in the case of pellagra in children, where the drugs 
seem to do some good, but it must be taken into consideration that 
pellagra in children is usually a trivial disease. Pellagra cannot 
be cured by either of these preparations of arsenic, but both may 
disturb a digestion which is already badly deranged. It is wisest 
to consider both drugs contraindicated and to begin no treatment 
until the hypodermic plan can be instituted. 

No phase of the treatment of pellagra is so important as the 
diet. This matter has never received the attention which its 



TREATMENT 345 

importance deserves. We note that Manson * strongly emphasizes 
the importance of diet in sprue above every other consideration. 
It has been noted on another page that there is a strong similarity 
between pellagra and sprue. The treatment of diarrhea and 
stomatitis form the greatest difficulty in the treatment of pellagra 
just as in sprue. It has been impressed on me repeatedly that 
absolute rest and a strict milk diet would do great good in 
pellagra, just as in sprue. Certainly rest in bed is the best way 
to conserve the little strength of the cachectic patient, and it also 
has a most pleasing effect on the diarrhea. In sprue Manson 
directs that the patient take the milk very slowly through a straw 
or from an infant's feeding bottle. In the beginning sixty ounces 
is the limit of the amount of milk allowed in twenty-four hours. 
This would be too large an amount in the beginning in pellagra. 
Manson increases this amount until one hundred ounces are taken. 
All other forms of food are withheld and the patient is kept on 
this diet- for six weeks after the mouth heals and the stools become 
solid. This plan with slight modifications is the best for pellagra. 
As the stomach is usually affected and there is decided anorexia, 
it is well to begin with not more than a pint in the twenty-four 
hours and increase one ounce with each feeding until a sufficient 
amount is taken to supply the number of calories needed. It 
should be remembered that many pellagrins go for weeks with 
practically no food. It is unfortunate that so few of our patients 
among the rural population of the southern states will take milk. 
It would be well if the next generation would learn to take milk 
and to depend on it more largely than at present. If all our 
patients could be induced to take milk the problem of the treat- 
ment of pellagra would be greatly simplified, as it will be found 
that this diet is as effective in pellagra as in sprue. The extreme 
irritation and sensitiveness of the mouth causes the milk to be 
especially grateful. If it cannot be taken, it is well to try butter- 
milk. Taylor of Columbia has suggested the use of the Bulgarian 
bacillus in the milk. After the milk has been taken for some 

1 Manson, Sir P., " Tropical Disease," 1907. Also in Allbutt's " System of 
Medicine." 1905. 



346 A TREATISE ON PELLAGRA 

time and is well borne, a raw egg may be added to it, beating the 
two together thoroughly. The nutrition of the patient is a matter 
of as great importance as in tuberculosis and there can be no 
better food for this purpose than milk. If large tough curds ap- 
pear in the stools it is advisable to resort to peptonization, re- 
ducing the length of time of the process gradually. Manson advo- 
cates the use of fruit juices in sprue; I have not yet tried this 
plan in pellagra. If milk in all its forms fails it is well to resort 
to a broth composed of a meat, as beef, mutton, or chicken, and a 
cereal, as barley, rice, or oatmeal. It is well to prepare the meat 
broth and the cereal broth separately and mix the two at the time 
of using. It is also well to vary the diet day by day by a rotation 
in the kind of broth so that the patient will not tire. It is im- 
portant not to depend on this diet but a short time, as it is not 
sufficient and the patient will lose weight on it, even though the 
attack is subsiding. As soon as the diarrhea subsides it is well 
to begin with the regulation semi-solid diet. Often a patient who 
cannot or will not take milk will take milk toast, and it forms a 
very suitable food. Later rare beef, Avhite potatoes, dry toast, and 
foods of this class are in order. It has been my rule to withhold 
all vegetable and fruit food until the symptoms have all subsided. 
As the disease usually appears in the spring, it is important to 
warn the patient against the use of all new vegetables and early 
fruits, as strawberries. 

It is customary to instruct the pellagrin not to eat corn food 
in any form, but so many of my patients have never eaten this 
form of food that this advice is often superfluous. In others 
who are sceptical about the connecting of this much-abused Ameri- 
can cereal with the etiology, this advice is ignored and I have 
never been able to see that they fared any differently from the 
patient who never ate maize at all. It is still a routine thing 
to advise that no corn be eaten, and will be until a definite con- 
clusion is reached regarding the true cause of the disease. 

When vomiting is troublesome or in those cases in which it is 
impossible to get the patient to take food it is often helpful to 
resort to proctoclysis, using normal saline solution. Some ob- 



TREATMENT 347 

servers have advocated this as a curative measure of decided bene- 
fit, but the yearly recurrence in most cases has soon dispelled this 
idea. This plan will usually fail if the rectal tenesmus is marked. 

Alcohol or some of the proprietary foods composed chiefly of 
alcohol have been used, but in my experience have proven harmful, 
and there seems a definite contraindication to the use of any 
form of drug or food of this class. 

For the diarrhea I have tried a preparation described by Tennen- 
baum * under the name " almateina." It is a synthetic product, 
claimed by the chemist Lepetit to be produced by the action of 
formaldehyde on hsematoxylon. It occurs in a fine powder of 
a dark red color. It is given in doses of seven and a half grains 
(0.5 grams) every three or four hours. This drug is claimed to 
relieve many forms of diarrhea, but in this disease it has not 
been uniformly successful. Some of my colleagues have reported 
favorable results from its use, but the number is not large. There 
is no drug in the Pharmacopeia that will relieve the diarrhea 
of pellagra. Any attempt to produce such a result always results 
in failure and usually the measure is otherwise hurtful to the 
patient. It would be well if the use of so much bismuth was 
abandoned, as it never does good, and an impure preparation 
theoretically would be contraindicated, especially in pellagra, on 
account of the mouth condition. Until the underlying condition 
is relieved or subsides nothing will benefit the diarrhea or the 
stomatitis. For the stomatitis simple cleanliness is the best plan 
of treatment. This may be supplemented with some simple astrin- 
gent, if desired, and in some cases a dilute solution of peroxide 
of hydrogen may be used as a mouth wash. A. E. Alford of 
Greensboro, North Carolina, has told me of his success in the use 
of such silver salts as argyrol, both on the skin lesions and 
by mouth, for the stomatitis and gastro-intestinal condition. This 
would deserve further trial. 

For the skin lesions I have never found an application that 
would do any good. The condition may well be compared to the 

1 Tennenbaum, H., " Ein verlaessliches Antidiarrhoillum." Zentralb. fur 
innere Med., 1909. 



348 A TREATISE ON PELLAGRA 

skin lesion of small-pox, which will subside at a certain time, 
regardless of, or in spite of, treatment. In small-pox all that can 
be done is to protect the skin and keep it in good hygienic con- 
dition. So also in pellagra after the use of sufficient soap of a 
bland character and warm water followed by a simple protecting 
unguent, as petrolatum or lanolin, all that is possible has been 
done. Babcock recommends the following : 

Pulv. calamine 4 drams Rose water 2 ounces 

Pulv. zinc oxide 3 drams Lime water to make . . 1 pint 

This is to be applied freely at short intervals. This same 
observer also employs the following: 

Pulv. calamine % dram Olive oil % dram 

Zinc oxide % dram Lanolin to make 1 ounce 

It is important to consider the sleeplessness and nervous irri- 
tability which exhausts so many patients. For these conditions 
such drugs as trional and veronal, as well as chloral and paralde- 
hyde, have been employed. I have been especially successful with 
chloretone, which has the great advantage of being sedative to the 
stomach in cases of nausea and vomiting. 

For the pain of a lancinating character ISules recommends five- 
grain doses of acetylsalicylic acid four times a day. For the 
severe pains in the hands and feet I have never found any remedy. 
Even opiates are very unsatisfactory. 

It was hoped that transfusion would be the great remedy in 
the treatment of pellagra. After a thorough trial the results are 
rather discouraging. I have seen it done twice : once by T. M. 
Green of Wilmington, North Carolina, and once by J. W. Long 
of Greensboro, North Carolina. In both instances the recipient 
was in an extreme condition and the donor was a healed pellagrin. 
Both donors were poor subjects, but were the best at hand. One 
of these, at least, was heavily infected with hookworm and the 
hemoglobin was quite low. The other was not much better. In 
both cases death followed in the course of about the same time that 
we would otherwise have expected. 



TREATMENT 349 

H. P. Cole and G. J. Winthrop of Mobile have done quite a 
number of transfusions and their results have been more encour- 
aging. Their conclusions were as follows : 

(1) Transfusion offers a means of combating the anemia, 
stimulating the recuperative functions and perhaps of furnish- 
ing antitoxic substances to pellagrins. 

(2) The lessened mortality and marked improvement in trans- 
fused pellagrins leads us to anticipate the establishment of a serum 
therapy in the disease. 

(3) Transfusion may be offered as a surgical therapeutic pro- 
cedure in pellagrous cases, pending the perfection of a successful 
serum therapy. 

These observers were working on the assumption of the cor- 
rectness of such authorities as Antonini and Mariani, who claimed 
that a definite immunity is developed in a healed pellagrin and 
that the serum has a definite antitoxic action against maize poison- 
ing. Cole and Winthrop then conclude thus: 

(1) Pellagra is an intoxication. 

(2) The toxic principles of pellagra exist in the blood of pella- 
grins and will produce pellagrous symptoms when transferred to 
other animals. 

(3) Pellagrous serum exhibits definite precipitative, hemolytic, 
and antitoxic properties. 

(4) An artificial immunity can be produced in animals and 
exists in cured pellagrins. 

All of this work is based on an assumption that damaged maize 
causes pellagra. This is not generally accepted, and since I be- 
gan this work the number who reject the theory has greatly in- 
creased. Until this problem of the cause is determined, little 
work of this kind can be done along this line. In the meanwhile 
blood transfusion is empirically indicated when other measures 
have proven ineffective and when a suitable donor can be had. 
A suitable donor may be had from the non-pell agrous as well 
as from the pellagrous. Recent work has shown that a previous 
history of pellagra does not render an individual a more desirable 
donor than otherwise. This would tend to show that there is 



350 A TREATISE ON PELLAGRA 

not that specificity of the blood serum which has been supposed 
to exist. 

Hydrotherapy has been stressed by various writers on pellagra 
and it is probably of some service, especially as a placebo when 
it can be administered in an institution especially equipped for 
the purpose, employing trained attendants. Unless given with 
great care and particular attention to the individual condition of 
the patient, there would be a definite contra-indication. For my 
own part I would prefer the salt bath or rub, especially in the 
neurasthenic type of the disease. This rub is very simple, and 
may be given anywhere without the necessity of going to an 
institution. It must be considered in advising any general line 
of treatment that the large majority of these patients live in the 
country and are usually poor, hence treatment must as far as possi- 
ble be adapted to the conditions, for the reason that, like syphilis, 
pellagra requires about three years of treatment before the patient 
can be safely discharged. In some cases in which the restlessness 
is very marked the hot bath cautiously given will prove sedative. 
The cold bath should be given with unusual caution. Medicated 
baths, chiefly of arsenic and sulphur, have been tried, but no very 
signal improvement has been recorded from this plan of treat- 
ment. The special indication in this latter plan is certain con- 
ditions of the skin and also in intestinal conditions more par- 
ticularly when attended with marked wasting. 

Much attention should be paid to the general hygienic condi- 
tions. While pellagra may occur in the most robust and the 
best nourished, it is a well recognized fact that it finds a most 
favorable soil in debilitated people of all ages. It has been men- 
tioned that the presence of hookworm disease is a predisposing 
cause and that the eradication of this condition will largely re- 
lieve the pellagra situation. It must be held in mind that this 
is only one of the predisposing causes which may be treated. 
Pellagra occurs many times among the better classes, who would 
never be suspected of living in anything but a good hygienic 
condition. This is especially true of old people living alone. 
They often pay too little attention to their nourishment and in 



TREATMENT 351 

some instances unconsciously become dependent on alcoholic stimu- 
lation. In my judgment alcohol is the most constant single pre- 
disposing factor in pellagra and many of the so-called cases of 
pseudo-pellagra attributed to alcoholism are really pellagra. I 
recently saw by accident an old gentleman in good circumstances 
who was nursing sore hands and who had suffered for a long 
time with diarrhea. His mental condition was counted an in- 
firmity of advancing years. He was not a consumer of maize, 
but he had a typical case of pellagra. A general debilitated con- 
dition predisposed to this trouble and more attention to his per- 
sonal hygiene and diet might have given him the resistance needed 
to combat the disease. 

Change of climate in pellagra will do fully as much as in 
tuberculosis. In time it will be generally recognized as important 
as in tuberculosis. As a rule cooler climates with short hot sea- 
sons and long winters are thought to be beneficial. Bass re- 
ported twelve cases sent to a cool climate and Xiles had four 
cases treated the same. In all the improvement was quite marked 
as well as prompt. Bass suggests the use of an artificially re- 
frigerated ward for the purpose. In my experience it is not 
altogether the cool climate which does the good, but also the 
general effects of a change of any radical kind, though I recall 
the fact that in many travels through the mountains of Xorth 
Carolina I never encountered a case of pellagra, in spite of the 
fact that a constant search was made. Cases of pellagra have 
occurred in Asheville, but as a rule they were sporadic and were 
brought in from a distance. In some instances the seashore is 
of decided benefit, but the essential thing is to have a radical 
change. It is a notable fact that cases of pellagra sent from the 
South where there was no improvement secured will often make 
the most rapid and marked improvement in the institutions of the 
Xorth, even though no special line of treatment is instituted. 
I have known patients advanced to the point of decided mental 
change to be entirely relieved in a. few weeks in such an insti- 
tution. This improvement is always indicated by a rapid gain 
in weight. This gain in weight, as previously mentioned, is as 



352 A TREATISE ON PELLAGRA 

important as it is in tuberculosis and is as reliable an indicator 
of the improvement. As long as a pellagrin gains weight the 
case is to be counted on the improvement side of the scale. 

In no class of cases does kindly encouragement mean so much. 
If the patient knows the nature of the disease he should be told 
how many recoveries are being made and should be given the im- 
pression that it is only a question of how long it will require to 
effect a cure and how cooperative he will be. These patients will 
try the patience of the most long-suffering with their hypochon- 
driacal manifestations, but there is no class of cases who are 
so grateful for help, and they will invariably " return to give 
thanks." Certainly no class of people will appeal so strongly to 
the humane medical man as the pellagrin, for in no disease is 
there found such a picture of abject despair. 

While the progress in the treatment of pellagra has been slow 
and there remains much to be desired, a consideration of the old 
Italian literature is sufficient to prove that much progress has 
been made. Until only a few years ago all writers stated posi- 
tively that it was a hopelessly incurable disease and that all 
remedies were equally unavailing. It is interesting to read the 
difficulties encountered by Gaetano Strombio, the greatest of all 
pellagrologers, in his efforts to find a cure. He tried a remedy 
which he had introduced for the treatment of elephantiasis and 
leprosy in pellagra. This remedy was a snake broth ! He also 
.used Spanish fly with no result. As he found all remedies tried 
by him to be without result, he went to celebrated physicians of 
the time for help and advice. One advised the plan of one Doctor 
Galli, which consisted in the use every morning of the juice of 
water cress, to which was added one ounce of honey and a small 
amount of the pulverized eyes of the lobster; to this was added 
a little arnica mixed with spirits of ammonia. The diet was 
advised to be entirely animal, and everything that would create 
acid Avas to be avoided. Balserei, another to whom Strombio 
applied for advice, had never had any experience, but advised 
turpentine oil to bring up the nerve strength, and he also recom- 
mended pine shoots macerated and used for the bath. Odoardi 



TREATMENT 353 

was said to have been successful with powdered whole lizards. 
Strombio considered the seat of the disease to be the abdomen, 
and therefore resorted to the use of purgatives to remove the 
impurities. He also used koumiss, rhubarb, and tamarinds, and 
hoped to reduce the number of stools. 

Pellagra can no longer be counted among the incurable maladies. 
There is as much hope of success in its treatment as in many other 
diseases which are counted far less malignant. It is not a self- 
limited disease, and unless vigorously treated from the beginning 
the same result must be expected as in improperly treated syphilis. 
The therapeutic nihilist has no more right to treat pellagra than 
to treat syphilis. 

Finally the fact must be emphasized that the most successful 
treatment of pellagra consists in the early diagnosis. 



INDEX 



Abbasia asylum, pellagra in, 33. 

Abdominal sympathetic system, 
changes in, 240. 

Abortion in pellagra, 157. 

Abscess of the liver, 219. 

Absence, of corn from dietary in 
pellagra, 74; of edema (differ- 
entiation from beri-beri), 38; of 
erythema, on ends of fingers, 170; 
of wine, a cause of pellagra, 56. 

Acarus farinae, distinction of, from 
corn mold, 64. 

Accumulation of electric fluid in 
blood, a cause, 53. 

Acetylsalicylic acid, 348. 

Acid intoxication, 96. 

Acidity of corn, tests for, 95, 96. 

Acidosis, 96. 

Acrodynia, 17, 38, 206, 297, 298. 

Actinic rays, a cause of pellagra, 50. 

Acute ascending paralysis, 251. 

Acute grain poisoning, 75. 

Acute nephritis, 162. 

Acute pellagra, 85, 302. 

Adami, 227. 

Adaptation of pellagra, 301. 

Addison's disease, 237. 

Adulteration of flour with meal, 73. 

Aestivo-autumnal malarial parasites, 
289. 

Affectless stupor, 270. 

Africa, pellagra in, 27. 

Ages, affected by pellagra, 120. 

Agostini, 127, 216. 

Alabama, pellagra in, 30; death 
rate in insane institutions in, 305. 



Albera, 2, 20, 50, 52, 53, 126. 

Alcaniz, pellagra in, 10. 

Alcohol, effects of, on pellagra, 107, 

123, 306; treatment with, 346. 
Alcoholic extract from polenta cul- 
tures, effect of, 70. 
Alcoholic paralysis, 261. 
Alcoholism, 284. 
Aldehyde-like substance in damaged 

corn, 93. 
Alessandri, 99, 109. 
Alford, A. E., 347. 
Alibert, 21. 

Allbutt, T. C, 208, 278, 308. 
Alleman, 261. 
Allen, William, of Charlotte, N. C, 

126, 220, 287. 
Almateina, 347. 
Alphas, 5. 

Alpine scurvy, 9, 108, 209. 
Alsberg, 324; Black and, 95. 
Ambulatory automatonism, 259. 
Ameba in pellagra, 126. 
Amebiasis, 126, 160, 219, 220, 287, 

306. 
Amebic dysentery, 162, 287. 
Amelioration of symptoms from 

change of diet, 73. 
Amenorrhea and pellagra, 157. 
Amentia, 271, 278, 279, 280, 285. 
American Indians, pellagra in, 27. 
Ammoniac, exhalation of, a cause of 

pellagra, 52. 
Amniotic infection with pellagra, 128. 
Amyotrophic lateral sclerosis, 250. 
Analogy between pellagra and Rocky 



356 



INDEX 



Mountain fever, trypanosomiasis, 

Kala-azar, etc., 290. 
Anaphylactic deviation of the com- 
plement, 94. 
Anaphylaxis in infection with the 

strepto-bacillus pellagra? (Tizzoni), 

88. 
Anderson, 134. 

Anemia, in dogs, 75; of brain, 239. 
Anesthesia in acrodynia, 298. 
Animal, parasitic, cause of pellagra, 

72, 290. 
Ankle clonus, 137. 
Ankylostomiasis, 107, 125. 
Annual recurrence of erythema, 198. 
Anomalies of genital organs, 127. 
Anorexia in man, 77. 
Antenatal pellagra, 129. 
Anticipatory treatment, 330, 336. 
Antiquity of pellagra, 1, 2, 45, 46. 
Antitoxic substances in pellagra, 349. 
Antitoxin, specific in pellagra, 91. 
Antizeists, 57. 
Antonini, 91, 278. 
Anxiety, 264; for sins, 148; 

psychosis, 273. 
Anxious delirium, 241. 
Apathetic state, 265, 277. 
Appearance of skin manifestations, 

163; of symptoms, order of, 150. 
Appendix fasciola, 173. 
Aqueous extract of spoilt corn, 67. 
Arachnitis, 228. 
Arachnoid in pellagra, 239. 
Ardor urinse, 156. 
Ardusset, 24. 

Areas of endemicity, 113, 135. 
Argentine Republic, pellagra in, 27. 
Argyrol, 347. 
Arioxide, 334. 
Arsenic, 74, 258, 303, 328; Fowler's 

solution, 338, 344. 
Arsenite, of iron, 335. 



Arterio-sclerosis, 236, 254, 306. 

Arylarsonates, 331, 337. 

Asheville, North Carolina, pellagra 

in, 115, 351. 
Asia, introduction of maize from, 100. 
Asia Minor, pellagra in, 27. 
Aspergillary infection of lungs, etc., 

92. 
Aspergillus fumigatus and flavescens, 

67, 75, 91, 92, 99. 
Assam, scurvy in, 46. 
Association, memory, 279. 
Astruc, 6. 
Asylum stage of pellagra, prognosis 

of, 308. 
Asymmetrical skin lesions, 164, 198. 
Asymmetry of face, 127. 
Atavism, 127. 

Ataxia, 137, 284, 334; static, 256. 
Ataxic, gait, 256; paraplegia, 254. 
Atlanta, pellagra in, 131. 
Atlantic Ocean, pellagra on coast of, 

115. 
Atmospheric effect on corn, 56. 
Atoxyl, 74, 158, 330, 331; in try- 
panosomiasis, 334; of French, 337; 

of Germans, 337. 
Atrophy, of the brain, 239; of the 

horny layer of the skin, 199; of 

the skin, 195, 200, 201; of the 

subcutaneous fat and muscles, 

149. 
Attitudes, grotesque, 259. 
Atypical pellagra, 164, 286, 290; 

skin lesions, 178; manifestations, 

202. 
Austria, pellagra in, 41, 108. 
Autointoxication theory of pellagra, 

91, 93. 
Autopsy findings on dogs, poisoned 

with pellagrosein, 80; on pella- 
*■'-., grins, 124,219; on rat poisoned 

with pellagrosein, 97. 




INDEX 



357 



Autumnal, recrudescence of ery- 
thema, 193; recurrence, 132. 
Aversion to activity, 148. 
Aviano, 20. 

Babcock, J. W., 25, 34, 43, 48, 210, 

331, 337, 348. 
Babes, 114, 145, 236, 240, 331, 334; 

and Manicatide, 91; and Sion, 

65, 201, 237, 277; Veselin, and 

Georghus, 334. 
Babinski reflex, 248, 251. 
Bacillus coli communis, 71, 91, 98. 
Bacillus mesentericus vulgaris, 68, 71. 
Back, lesions of, 147, 181. 
Bacterium maidis, 68, 71, 75, 85, 91, 

93. 
Bacterium thermo, 68. 
Baillarger, 261, 285. 
Bakeries, rural, 323. 
Balardini, 59, 67. 
Bald tongue, 211. 
Balling of polenta, 87. 
Balp, 109. 

Barbadoes, pellagra in, 27. 
Barbanti, Doctor Carlo, 47. 
Bardin of Petersburg, Virginia, 218. 
Barth, 251. 

Bartonville hospital, pellagra in, 36. 
Baserei, 352. 
Bass, C. C, 289, 351. 
Bassae, 251. 
Batalla, 16. 

Bed bugs and pellagra, 313. 
Bellamy, R. H., 33, 122, 184, 313. 
Belluno, pellagra in, 108. 
Belmondo, 136, 139. 
Bemis of New Orleans, 29. 
Beri-beri, 38, 94, 125, 133. 
Bertheim, 331. 
Bessarabia, pellagra in, 108. 
Beyris, 24. 
Biett, 21. 



Bigger, I. A., of Rock Hill, South 

Carolina, 163, 308. . 
Billod, 24, 49. 

Biologic deviation of the comple- 
ment, 94. 
Bismuth, in treatment of pellagra, 

347. 
Black and Alsberg, 95. 
Blastomycosis, 295; similarity of, to 

pellagra, 184. 
Blebs in pellagra, 186, 189, 190, 201. 
Bleeding of gums in pellagra, 209. 
Blindness from atoxyl, 333. 
Blockley Hospital, pellagra in, 36. 
Blood in peUagra, 71, 72, 150, 227, 

290; in vomitus of pellagrins, 217; 

strepto-bacillus pellagrae in, 85. 
Blood vessels of the nervous system, 

237. 
Blumenthal, 332. 
Boerhaave, 52. 
Boismont, Briere de, 21. 
Boliano, dictionary of, 11. 
Bona, 6. 
Bonafous, 58. 
Bondurant, 30. 
Bonnet, 23. 

Bosnia, pellagra in, 108. 
Botto, 134. 

Bouchard, 27, 54, 204, 229. 
Bower, Cuthbert, 31. 
Brachycephaly, 127. 
Brain, pathologic changes in, 228. 
Brava, Doctor, 47. 
Brazil, pellagra in, 27. 
Breakfast, of the Southerner, 73. 
Brianchi, 103. 
Brianza, 108. 

British Medical Association, 36. 
Broglio, hospital at, 2. 
Bronchitis, acute, 306. 
Bronzing of the skin in pellagra, 198. 
Broth, mixed, in pellagra, 346. 



358 



INDEX 



Brown atrophy of the liver, 222, 
Brown pigmentation, 171, 205. 
Bryce Memorial Hospital, 30, 305. 
Buccal mucosa in pellagra, 145; 

ulcer, 210. 
Buckwheat, 94. 

Buffalo fly, 115, 312. See Simulium. 
Bulgaria, pellagra in, 27, 108. 
Bulletin of the Illinois State Board 

of Health, 180. 
Bullock, E. S., 295. 
Burning, in the epigastrium, 148, 

255; sensation of, 257. 
Burns, confusion of, with pellagra, 

296; resemblance of, to pellagra, 90. 
Buzzard, 251. 

Cachexia, 144, 163, 285. 

Cachexy, 27. 

Cairo, death rate from pellagra in, 32; 
pellagra in, 32, 41. 

Caldarini, 156, 259. 

Calor del Higado, 14. 

Camara bales, 178. 

Campaign against pellagra in Italy, 
39. 

Camurri, 291. 

Cancer, 3. 

Cardiac disease, 124. 

Cardialgia, 145. 

Casal, Gaspar, 7, 8, 9, 14, 49, 58, 101, 
165, 170, 189; collar, 172, 313. 

Castellani, 114. 

Cat, effects of pellagrosein on, 80. 

Catalepsy, psychical, 276. 

Catatonia, 280. 

Cattedre ambulanti, 321. 

Cause, of death in the Andersonville 
prison, 28; of erythema, 136; of 
non-recognition of pellagra, 45; 
specific, of pellagra, 84. 

Cellular changes in the central ner- 
vous system, 240. 



Ceni, 91. 

Central canal of the cord, 228, 235. 

Central neuritis, 241. 

Cerebellar changes in pellagra, 238. 

Cerebral, changes, 238, 262; soften- 
ing, 240. 

Cerebro-spinal, disturbances, stage 
of, 144, 147; fluid, strepto-bacillus 
pellagrse in, 85. 

Ceresoli, 323. 

Cerri, 9, 108. 

Cesati, 67. 

Chalmers, 114. 

Changes of diet in pellagra, 73. 

Character, of corn, 64; of kernel of 
corn, 64; of pellagrosein, 65; of 
pellagrous e^thema, 197, 202; of 
spoilt corn, 64. 

Characteristics, of pellagra, 120; 
of strepto-bacillus pellagrse, 86. 

Chardon, 297. 

Charlotte, pellagra in, 131. 

Chart, temperature, of pellagra, 142. 

Chemical, rays of sunlight, 94; 
studies on maize, 64. 

Cherokee Indians, 27. 

Chicken, diminished sensibility for 
pellagrosein in, 79; spoilt corn and, 
76; variation of symptoms in, 
caused by various corn products, 
80. 

Chorea, 250; partial, 259. 

Choreiform, movements, 277; in 
chicken, caused by spoilt corn, 82. 

Christoferitti, 122, 128. 

Chromatolysis, 240, 241. 

Chronic nature of pellagra, 120. 

Cicatrization in pellagra, 190. 

Cinquantino, 321. 

Circular insanity, 148. 

Cirrhosis of liver, 216. 

Clark's column, cell changes of, 237; 
displacement of, 235. 



INDEX 



359 



Class of people affected, 130, 131. 

Classification, of pellagra, on path- 
ologic basis, 72; of Strachan's 
disease, 38. 

Climatic changes in pellagra, 51, 351. 

Clonic, contractions, 309; spasm, 
258, 262, 276. 

Clonus, ankle, 137. 

Coalescence of pustules in pellagra, 
190. 

Cochin-China diarrhoea, 162. 

Cole, H. P., 349. 

Collapse, acute, 285. 

College of Physicians and Surgeons 
of Philadelphia, Transactions of, 
241. 

Colon, ulcer of, 218, 219. 

Color of affected skin in pellagra, 
147, 192. 

Columbia, National Pellagra Con- 
ference, 35; pellagra in, 131. 

Commission, Tennessee Pellagra, 44. 

Common colon bacillus, 91. 

Communicability of pellagra, 133. 

Comparison of pellagra mortality rate 
in Europe and America, 305. 

Complement fixation, 289. 

Complications of pellagra, 214. 

Conclusions, of Marie, on pellagra in 
animals, 76; of Tizzoni, on strepto- 
bacillus pellagra?, 89. 

Concomitant maladies, 124. 

Condemnation of bad corn, 324; 
of valuable food stuffs, 119. 

Conditions, of maize culture in 
North Carolina, 74; of the negro 
in the South, 130. 

Confusion, 284. 

Confusional insanity, 285. 

Congenital, pellagra, 128, 143; psy- 
cho-physical weakness, 127. 

Congestive chill, 342. 

Conjunctivitis, 334. 



Consciousness, loss of, 149, 256. 
Constancy of maize consumption in 

the South, 73. 
Constipation in pellagra, 164, 220. 
Contagiousness of pellagra, 133. 
Contents of blebs, 188. 
Contraction, 277, 284; tonic, of 

muscles, 137. 
Contractures, 258; of flexion and 

extension, 260. 
Conviction of unpardonable sin, 148. 
Convulsive movements of single 

limbs, 256. 
Cook County Hospital, pellagra in, 

36. 
Coordination in pellagra, 253. 
Corium in pellagra, 189, 190, 191, 199, 

200. 
Corn, cultivation of, 324; meal, study 

of, 83; restriction of, from diet of 

pellagrins, 346; theory of pellagra, 

313; whisky and pellagra, 73. 
Corpora amylacea, 235. 
Cortical epilepsy, 149. 
CostaUat, 17, 25, 61. 
Cotton, H. A., 35, 241, 245. 
Cotton seed oil and pellagra, Mizell's 

theory, 118, 313. 
Cramps, 256. 

Cretanoid, dystrophic, 128. 
Criminal tendencies, 284. 
Criterion of cure, 329. 
Croatia, pellagra in, 108. 
Crowell and King, 342. 
Crumbine, Dean of the University 

of Kansas, 117. 
Crusts of skin in pellagra, 192. 
Cuboni, 68, 69, 72. 
Cultivation of maize, 324; in North 

Carolina, 74. 
Cultural peculiarities of the strepto- 

bacillus pellagra?, 87. 
Curative diet in pellagra, 318. 



360 



INDEX 



Cure, criterion of, 329; time limit of, 

in pellagra, 147. 
Cutting, W. Bayard, Jr., Consular 

Report of, 43, 313, 316. 

Da Gama, Vasco, 48. 

Dalmatia, pellagra in, 108. 

Danger of atoxyl, 332. 

Date of Casal's writings, 9. 

Deaths from pellagra, 304; in Cairo, 
32; in Italy, 40; in North Car- 
olina (Map), 116. 

Debilitating affections and pellagra, 
124. 

Debility in pellagra, 107. 

Decomposition, of albuminoids and 
hydrocarbons by the bacillus mai- 
dis, 71; of atoxyl, 335. 

Defecation, spontaneous, 260. 

Defibrinated rabbits' blood, culture 
medium for the strepto-bacillus 
pellagrae, 86. 

Deficiency, of gluten, 57; of vegeta- 
ble food in pellagra, 57. 

Definition of pellagra, 120. 

Deformities, 259. 

Degeneracy, 130. 

Degeneration, of the spinal cord, 
areas of, 229; reactions of, 259. 

Degenerative processes of the spinal 
cord, 229. 

De Giaxa, 91. 

Deiaco, 178, 180. 

Delay in results from atoxyl, 335. 

Del Campo, Higino, 14, 53. 

Delirium, acute, 276, 278; anxious, 
234, 241, 271, 277. 

Delia Bona, 45. 

Delusions, 275, 277; of grandeur, 263; 
of persecution, 263. 

Del Valle, Antonio, 14. 

Del Villahoz, Perrote, 17. 

Demarcation, line of, in mouth, 210. 



Dementia, 276, 284, 285; acute or 
stuporous, 265, 271; paralytica, 
149, 226, 242; praecox, 28. 

Department of Agriculture, on maize 
as a food, 62. 

Depression, attitude of, 148, 264, 277. 

Depressive type of psychosis, 263. 

De Rolandis, 134. 

Dermatitis, exfoliativa, 192; of pella- 
gra, 184, 186. 

De Salvanes, 17. 

Descending neuritis, 334. 

Desquamation, in pellagra, 129, 192, 
195, 200; of horny layer, 201. 

Detection of bad corn, 75. 

Deterioration of maize, test for, 65. 

Determination of the toxicity of corn, 
95. 

Deviation of the complement, 94. 

De Villarejo, 17. 

De Wolff, J., 27. 

Diabetes, 124. 

Diagnosis of pellagra, 146, 271, 286; 
importance of early, 353; impor- 
tance of skin lesions in, 291. 

Diarrhoea, from sporisorium maidis, 
67; in dogs, 77; in mental dis- 
orders other than pellagra, 263; 
in pellagra, 126, 127, 136, 145, 150, 
163, 192, 195, 204, 214, 220, 221, 
271, 286, 347; of spoilt maize, 75. 

Dictionary of Boliano, 11. 

Di Donna, 91. 

Diet, curative, 318, 335, 345. 

Dietary of southern people, 73. 

Difference, between pellagra and 
alcoholism, 299; between pellagra 
and paralysis, 299; between pella- 
gra and syphilis, 288; between 
pellagra and trypanosomiasis, 298; 
between soamin and atoxyl, 337. 

Differential leucocyte count, 151. 

Differentiation, of pellagra and 



INDEX 



361 



pseudo-pellagra, 49, 61; of pella- 
gra and psilosis pigmentosa of 
Barbadoes, 31; of pellagra and 
purpura, 196; of pellagra and 
scurvy, 50. 

Digestive, disturbances, 146, 208, 
217, 286; origin of pellagra, 208. 

Dilatation of stomach, 216. 

Dilopus febrile, 107. 

Diminution of urea, 157. 

Diseases predisposing to pellagra, 123. 

Disfigurement in pellagra, 190. 

Disgust for food, 215. 

Disinclination to work, 144. 

Dispensary plan of treatment, 319. 

Distinction between pellagra and 
psilosis pigmentosa of Barbadoes, 
31. 

Distinctive features of the erythema, 
146. 

Distractibility, 279. 

Distribution, between organic and 
functional basis of nervous symp- 
toms, 247; geographical, 1; of 
skin lesions, 167. 

Disturbances of speech, 299. 

Dizziness, 144, 255. 

Doering, 46. 

Dogs, effects of pellagrosein on, 80. 

Dolicocephaly, 127. 

Donovan's solution of arsenic, 344. 

Dosage of arsenic preparations, 338. 

Drewry, 152. 

Drinking water of pellagra districts, 
99. 

Droopiness in dogs, 77. 

Dry skin lesions, 186, 192. 

Drying of corn, artificial, 83, 321. 

Dupre, 77, 82. 

Dupuch-Lapointe, 23. 

Dura mater in pellagra, 239. 

Durham, North Carolina, pellagra 
in, 114, 131. 



Dyer, Isadore, of New Orleans, 30, 

184, 295, 328. 
Dysentery, 107, 124, 221; amebic, 

162, 287. 
Dyspepsia, 208. 
Dysphagia, 214; from spoilt maize, 

75. 

Early diagnosis of pellagra, impor- 
tance of, 304. 

Eczema, 202; of chickens' comb, from 
spoilt corn, 82; squamous, 295; 
vesicular, 184, 296. 

Edema, 150, 190. 

Effect, of damaged grain on animals, 
75; of light on atoxyl, 332; of 
polenta cultures on animals, 70; 
of sunlight on pellagra, 309; of 
surgical procedure on pellagra, 
310; of temperature on animals 
poisoned with pellagrosein, 80; 
of weather on corn, 324. 

Effusions, 150. 

Egypt, pellagra in, 32, 46, 60, 132, 
135, 286, 291. 

Elbows in pellagra, 171. 

Electric, chorea, 259; excitability, 
257; fluid, accumulation in blood, 
53; reaction, 256. 

Elephantiasis, 5. 

Ellia, 61. 

Emaciation, 195, 204. 

Emprosthotonic tetanus, 260. 

Endemic, 110; centres, 114; ery- 
thema, 197. 

England, pellagra in, 27. 

Enriques, Juan Andrez, of Fer- 
moselle, 12, 13. 

Enteritis, 137, 218. 

Eosinophilia, 126, 152. 

Epidemic, form of pellagra, 301; of 
Paris (acrodynia), 18. 

Epidemiology, 97, 113, 220. 



362 



INDEX 



Epigastric pain in pellagra, 127. 

Epilepsy, 250, 277; cortical, 149; 
pellagrous, 277, 299. 

Epileptiform attacks, 149, 156, 256. 

Epithelial layer in pellagra, 209. 

Epithelium of the tongue, 209. 

Epizootics, cause of, 107. 

Erba, 66; method of studying spoilt 
maize, 66. 

Ergotism, 49, 57,72, 96, 150, 197, 226, 
298. 

Eructations, 214. 

Erysipelas, 4, 124. 

Erythema, 50, 54, 145, 146, 168, 286, 
291; exudativum (Hebra), 187; 
in children, 173, 177; in dogs, 75; 
multiforme, 184, 186, 202, 205, 
206, 296; of female genitalia, 198; 
of lower extremities, 173; of peri- 
neal region, 198; of toes, 174; 
polymorphe, 202; toxic, 186. 

Esophagus, dryness of, 145, 214; 
heat in, 211. 

Estimate of pellagra in North Caro- 
lina, 37; in the United States, 327. 

Ethyl erythema, 107. 

Etiology, problem of, 2, 49, 327. 

Euphoria, 277. 

European centres, pellagra in, 10S. 

Eurotium herbariorum, 67. 

Exacerbations of erythema, 132. 

Exaggeration of reflexes, 137. 

Exaltation, 284. 

Exchange of good maize for bad, 323. 

Excitability, electrical, 257. 

Exfoliation of skin in pellagra, 146, 
185. 

Exhalation of ammoniac, a cause, 52. 

Exhaustion, 277. 

Existence of micro-organisms in 
sound corn, 83. 

Experiment, on cat, with pellagrosein, 
80; with verdet, 61. 



Experimental, production of pellagra, 
in guinea pigs, 85; use of atoxyl, 
334. 

Exudation in pellagra, 190. 

Eye changes in pellagra, 158. 

Fabinyi, 236. 

Face, lesions of, 147. 

Facheris, 52, 53, 127. 

Fagopyrism, 94, 197. 

Fall recurrence, 132. 

Fallacy of the maize theory, 102. 

Farado-cutaneous sensibility, 260. 

Farming class and pellagra, 131. 

Fatality of pellagra in childhood, 
122. 

Fatty liver, 222. 

Fear of insanity, 270; of unpardon- 
able sin, 276. 

Fearfulness in pellagra, 127. 

Features of erythema, 146. 

Feces of pellagrins, 69, 126, 160, 220; 
strepto-bacillus pellagrse in, 85, 88. 

Feet, skin lesions of, 147. 

Feijoo, 10, 16. 

Female genitalia, erythema of, 198. 

Ferments, role of, in production of 
pellagra, 84. 

Ferrati, Gosio and, 96. 

Fertilization with animal excreta, a 
cause of strepto-bacillary infec- 
tion of corn, 86. 

Fever, in pellagra, 138, 307; in sal- 
varsan treatment, 342. 

Field laborer, 131, 133; pellagra 
limited to, 106. 

Filariidse, 99. 

Filippi, 215. 

Fingers in pellagra, 170. 

Fiorini, 152. 

First pellagra hospital, 6. 

Fissures in the horny layer of the 
skin, 190. 



INDEX 



363 



Fixation of the complement in pella- 
gra, 289. 
Fixed idea, 269. 
Flarer, 158. 

Flema salada, 12, 16, 17, 60. 
Flexibilita cerea, 272. 
Flexures of extremities, 276. 
Fly districts in pellagra sections, 1 13. 
Food, refusal of, 75; value of maize 

as, 62. 
Foot lesions, 165, 167. 
Formentone, 100. 
Formications, 18, 144, 148, 255. 
Forms of hereditary transmission, 

127. 
Fowler's solution of arsenic, 338, 344. 
Fox and Darier, 205. 
Fox, Howard, 186, 240, 288. 
France, pellagra in, 22, 108. 
Frank, 134. 

Franzago, 20, 47, 56, 57, 239. 
Frapolli, 2, 3, 19, 50, 53, 131, 166, 

177. 
Fratini, 152. 
French atoxyl, 337. 
Frequence of maize consumption in 

the southern states, 60. 
Fulminating type of pellagra, 140, 

262, 303, 330. 
Functional nervous disturbances, 255. 
Fungoid growth on maize, a cause of 

pellagra, 61. 

Gait, in pellagra, 107; uncertain, 

127, 149, 256. 
GaUi, Dr., 352. 
Gangrene of the skin in pellagra, 30, 

192, 263. 
Gastralgia, 214. 
Gastric, hemorrhage, 217; secretion, 

258; symptoms, 136, 164. 
Gastritis, caused by sporisorium 

maidis, 67. 



Gastro-intestinal disturbances, 120, 

136. 
Gaumer, G. F., 292. 
Gauntlet, pellagrous, 171. 
Gavini, 152. 
General characteristics of pellagra, 

120; paralysis, 276, 277. 
Genital organs, anomalies of, 127. 
Geographical distribution, 1, 5, 132. 
Georgia, pellagra in, 29, 251. 
Georgopulos, 331. 
German atoxyl, 337. 
Gherardini, 2, 3, 4, 19, 50, 52, 131, 

134, 204. 
Gibelli, 75. 
Giddiness, 255. 
Gimeno, Dr., 11, 22. 
Gintrac, 23, 25. 
Glandular involvement in pellagra, 

189. 
Glisson's treatise, 45. 
Globus hysterica, 144, 148, 255. 
Glossina palpalis, 97. 
Glove-shaped area of erythema, 193. 
Gluten, insufficiency of, in maize, 62. 
Glutinous substance of spoilt corn, 

67, 77. 
Golgi, 236. 

Gordon's paradoxical reflex, 251. 
Gorizia, Heider and, 70. 
Gosio's test, 59, 96. 
Government ownership of grist mills, 

321. 
Grain intoxication, 72, 75, 133, 150, 

226. 
Granulating wound of the skin in 

pellagra, 189. 
Granulomata, infectious, 238. 
Gray, Dr. John, 29. 
Greece, pellagra in, 27, 108, 118. 
Green, T. M., 253, 348. 
Grief over imaginary sins, 263. 
Grifnni, 199. 



364 



INDEX 



Grimaldi, 237. 
Grimm, 118. 
Grist mills, 321. 
Grotesque attitudes, 259. 
Guerreschi, Dr., 21, 58. 
Gynecologic features of pellagra, 157. 

Habitat, of pellagra in North Caro- 
lina, 115; of simulium, 108, 114. 

Hair follicles in pellagra, 199, 200. 

Hallucination, 271, 279, 284; visual, 
137. 

Hallucinosis, 271. 

Hameau, 22, 58, 64, 134, 223, 237, 287. 

Handwriting, 273, 280. 

Hardy and Marchand, 168. 

Hargrove, W. F., 191. 

Harmlessness of bacterium maidis, 
69. 

Harris, H. F., 29, 209, 210, 216, 218, 
223, 237, 287. 

Headache in pellagra, 144, 148, 255, 
264. 

Heat isolation process for the strepto- 
bacillus pellagra, 89. 

Heat resisting properties of the bac- 
terium maidis, 69. 

Heart disease, 124, 150. 

Hebra's erythema exudativum, 189. 

H eider, 69; and Gorizia, 70. 

Hematemesis, 216. 

Hemorrhage, of the bowels, 191, 196; 
of mucous membrane, 196; of 
stomach, 217. 

Hemorrhagic form of pellagra, 196. 

Hereditary transmission, 112, 126, 
127, 128. 

Herpes iris and circinata, 206. 

Hesitation in pellagra, 265. 

Hiob, a hospital called, 3. 

Hippocrates, 4; of the Asturias 
(Casal), 11, 15. 

Hirsch, 46, 47. 



History of pellagra, 1. 

Homicidal tendency, 148, 282. 

Hookworm disease, 130, 306, 348; 
among negroes, 123; early account 
of, 27. 

Horny layer of the skin in pellagra, 
189, 190. 

Hospital, Bryce Memorial, 305; first 
for treating pellagra, 6; Hollen- 
Hagen, 21; Insane, of Buffalo, 35; 
Insane, of North Carolina, 36, 214; 
Insane, of New Jersey, 35; James 
Walker Memorial, of Wilmington, 
North Carolina, 126, 157; Kasr-et- 
Nil, of Cairo, 33; Majeur, of Milan, 
19; Marine, of Wilmington, North 
Carolina, 35; Mt. Vernon, 305; 
Philadelphia General (Blockley), 
36; Saint Andre, 24; Saint Louis, 
21; State of Peoria, 296; Turin, 
256. 

Hotel Dieux, 21. 

Howard, L. O., 114. 

Idea, fixed, 269; of persecution, 279; 
of sin, 273. 

Identity of American and Italian 
pellagra, 34; of pellagra and con- 
ditions in the lower animals, 72; 
of pellagra and mal de la Rosa, 
8, 9; of pellagra and pseudo-pella- 
gra in America, 61; of skin and 
tongue changes, 210. 

Igersheimer, 334. 

Ilium, ulcer of, 218. 

Illinois State Board of Health, 155, 
157, 160, 180, 209, 217, 219, 223, 
247, 251, 290, 305. 

Ill-temper, 144, 255. 

Illusions, 265, 284. 

Imaginary sins, 148. 

Immunity, artificial, 349; of doctors, 
etc., 134; of domesticated animals 



INDEX 



365 



to poison of maize, 92; of urban 

population, 133. 
Impetigo of Celsus, 5. 
Inanition, chronic, 75. 
Incapacity, mental and physical, 

264. 
Incendiarism, 285. 
Incontinence of bowel and bladder, 

150. 
Incoordination of motion, 149. 
Increase, in mononuclear elements 

of blood, 72; in weight and its 

indications, 307; of tendon re- 
flexes, 75. 
Indian corn, 2. See also Maize. 
Indicanuria, 157. 
Indifference, stolid, 264. 
Ineffectiveness of pellagra laws of 

1902 in Italy, 105. 
Infantilism, myxedematous, 128. 
Infectious granuloma, 238. 
Infective-exhaustive psychosis, 273. 
Infiltration, perivascular, round cell, 

290. 
Injection of papilla? of the tongue 

in pellagra, 145. 
Inoculation of monkeys, 118. 
Insane idea, 138. 
Insane institutions, pellagra in, 35; 

pseudo-pellagra in, 26, 27. 
Insanity, acute confusional, 271. 
Insect-borne parasitic disease, V, 

105. 
Insolation, 20, 53, 133, 134. 
Insufficiency, of gluten, 62; of maize, 

57, 61, 62. 
Intention tremor, 256, 258. 
Intercurrent diseases, 149, 306. 
Interference with thought, 148. 
Intermediate host, 5, 135. 
Intermittent fever and pellagra, 51. 
Intestinal, hemorrhage in chickens, 

from spoilt corn, 82; mycosis from 



spoilt polenta, 91; parasitic infec- 
tion, 126, 160; symptoms, 160; 
tract of dogs, 72; tract, pathology 
of, in pellagra, 217. 

Intoxication, acid, 96; disease, 71; 
grain, 72; psychosis, 273. 

Introduction of maize into Europe, 
100. 

Inunction of arsenic, 334. 

Irritable depression, 148. 

Itching, of back, 255; of backs of 
hands, 147, 255; of feet, 147; of 
lower extremity, 255. 

Jactitation, 272. 

Jakinow, W., 332. 

Jamaica, pellagra in, 37. 

James Walker Memorial Hospital, 

126. 
Jansen, 21. 
Jaundice, 127. 

Johns Hopkins Hospital, 157. 
Joseph II, of Austria, 6, 316. 
Jourdan, 22. 

Kala-azar, 46, 72, 125, 225. 

Kansas State Board of Health, 117. 

Kaposi, 206. 

Kasr-et-Nil Hospital in Cairo, 33. 

Katatonics, 260, 270, 271, 272, 280. 

Katonsky, 237. 

KeUy, H. A., 158. 

Kerr, Dr. W. J. W., 28. 

Kherson, pellagra in, 108. 

Kitchens, sanitary, in Italy, 318. 

Koch's, method of detecting try- 
panosomes, 290; postulates in in- 
fection with the strepto-bacillus 
pellagrae, 91. 

Labor situation in the South, 130. 

Lachaise, 26. 

Lack of salt, a cause of pellagra, 51. 



366 



INDEX 



Lactic acid in pellagra, 215; fermen- 
tation of spoilt corn, 67. 

Lalesque, 23. 

Lamellae, 200. 

Lamellated appearance of the ery- 
thema, 133, 196. 

Landouzy, 54, 204. 

Landry's paralysis, 251. 

Lassitude, 264. 

Lathyrism, 197. 

Lavacher, de la Feutrie, 21. 

Lavinder, C. H., 34, 104, 122, 133, 
134, 135, 136, 138, 154, 155, 304, 
305; and Anderson, 90; and Bab- 
cock, 38, 132, 141, 145, 158, 170, 
250, 259. 

Laws of 1902 regarding pellagra in 
Italy, 104; regulating corn traffic 
in Italy, 317. 

Leaping into the water, 255. 

Lecithin in complement fixation in 
pellagra, 289. 

Leichman, Sir William, 46. 

Lemaire, 25. 

Lepetit, 347. 

Lepra, fourth species of genus, 11. 

Lepra asturiensis, 4, 10. 

Lepra scorbutica, 5. 

Leprosy, 1, 3, 4, 5, 7, 190, 288. 

Leptomeningitis, chronic, spinal and 
cerebral, 228. 

Leuca of the Greeks, 5. 

Leucocyte count in pellagra, 151. 

Leucoderma, 195. 

Leucorrhoea, 157. 

Light, effect of, on atoxyl, 332. 

Ligurian mountains, pellagra in, 47. 

Limitations of pellagra, 133, 134. 

Line of demarcation of pellagrous 
lesions, 204. 

Lips, redness of, 145. I 

Liver, abscess of, 219; fatty, 222; in 
pellagra, 222. 



Locanda sanitaria, 112, 316, 319. 
Location of erythema on exposed 

parts, 146, 147. 
Locomotor ataxia, 237. 
Lombroso, 18, 56, 58, 62, 63, 65, 68, 

70, 71, 72, 84, 89, 140, 142, 215, 

238, 255, 276, 305, 328; and 

Peschel, 71, 77, 83, 127. 
London School of Tropical Medicine, 

162, 287, 327. 
Long, J. D., 36. 
Long, J. W., 348. 
Loss, of consciousness, 256; of 

sensibility, 75. 
Lower extremities, affection of, 165. 
Luckacs, 236. 
Lues, 150. 

Lunatics, pellagra in, 102. 
Lungs, aspergillary infection of, 91. 
Lupine disease, 197. 
Lusanna and Frua, experiments of, 

with verdet, 61. 
Lymphocytes, increase in, 290. 

Macules, discrete, in pellagra, 193. 

McBrayer, L. B., 222. 

McCafferty, E. L., 30. 

McKee, James, 36, 214. 

Maize, 56; culture medium for 
strepto-bacillus pellagra?, 85; in- 
troduction of, 2; precipitine, 291; 
theory of, 49, 312, 327. 

Majjochi, 68, 196. 

Maladie, de la Teste, 24; de l'insola- 
tion du printemps, 53. 

Malady of Paris, 297. 

Mai, d'Aerouse, 25; de misere, 55; 
del Higado, 11, 16; de la Rosa, 
2, 5, 7, 8, 10, 11, 12, 49, 53, 58; del 
Monte, 13, 16; el Monte, 13, 16; 
de la Saintes-Mains, 25; de Saint 
Amans, 25, 26; de la Sainte-Rose, 
25, 26; des Bascons, 25. 



INDEX 



367 



Malaria and pellagra, 30, 38, 113, 

123, 124, 125, 127, 135, 138, 152, 

225, 242, 263, 277, 289, 306. 
Malformation of the skull, 127. 
Malnutrition, a disease of, 55, 61; 

cause of electrical excitability, 

257. 
Malposition of external ear, 127. 
Manfredi, 158. 
Mania, 148, 276, 277. 
Manic-depressive insanity, 273, 280. 
Manifestations, nervous, 5. 
Manner, of infecting with strepto- 

bacillus pellagra?, 89; of living of 

Italian peasantry, 41. 
Manning, C. G., 31, 217. 
Manson, Sir Patrick, 36, 61, 97, 114, 

207, 212, 298, 345. 
Map of North Carolina, showing 

pellagra death rate, 116. 
Marasmus, 149. 
Marchand, 24, 54, 168. 
Mariani, 9, 236, 254, 306. 
Marie, E., 33, 65, 67, 68, 72, 75, 76, 

83, 122, 156, 192, 218, 256. 
Marine Hospital at Wilmington, 

North Carolina, 35. 
Marinesco, 237, 241. 
Martin, E. H., 327, 331, 337. 
Marzari, 9, 20, 45, 56, 57, 58, 62, 

127. 
Masini, 152. 
Mask, T. R., 29. 
Mask of face in pellagra, 193. 
Massachusetts, pellagra in, 46. 
Matterola, 75. 

Maurocordato, Prince Nicolas, in- 
troducer of corn into Europe, 26. 
Meal of spoilt corn, 64. 
Measles, 301. 
Mechanical, muscular irritability, 

260; skin irritation confused with 

pellagra, 171. 



Melancholia, 148, 226, 270, 271, 273, 
277. 

Melas, 5. 

Melega, 100. 

Melena, 217. 

Melica, 100. 

Memory, association, 297; distur- 
bance of, 284; weakness of, 270. 

Mendez-Alvaro, 11, 16. 

Meninges in pellagra, 240. 

Meningitis, 250, 285. 

Menorrhagia in pellagra, 157. 

Menstrual disturbances, 157. 

Mental, attitude, 148; confusion, 
278; depression, 195; insufficiency, 
270; symptoms, 208, 263; weak- 
ness, 144, 255. 

Mercurial ptyalism, 209. 

Merk, 120, 136, 167, 172, 173, 177, 
184, 187, 188. 189, 196, 200; 
table of ages by, 120. 

Merrill, T. C, 30. 

Mesenteric glands, aspergillary in- 
fection of, 92. 

Mesnil and Nicolle, 331. 

Mexico, pellagra in, 27, 76, 178. 

Meyer, Adolph, 241. 

Meynert's stuporous amentia, 279, 
281. 

Micrococcus thecalis, 252. 

Microscopic study of the skin in 
pellagra, 199. 

Micturition, spontaneous, 261. 

Milan, pellagra hospital at, 6; re- 
port on pellagra from, 43. 

Milk diet in pellagra, 345. 

Mixed infection in pellagra, 138, 
140. 

Mizell's theory of the etiology, 118, 
313. 

Mobile, pellagra in, 131. 

Mobley, J. W., 250. 

Modernity of pellagra, 1, 7. 



368 



INDEX 



Moist type of erythema, 139. 

Moisture, a cause, 52. 

Moldavia, pellagra in, 26. 

Molded corn bread, 67. 

Monkeys, experimental simulium in- 
oculation of, 118. 

Monomania, 276; systematic, 278. 

Mononuclear elements, increase of, 
72, 152, 290. 

Month of the year in relation to 
pellagra, 144, 209. 

Moral impressionability, 276. 

Morbus puerorum Anglorum, 45. 

Morelli, 240. 

Moriggia, 3. 

Morphaa Alguada of the Arabs, 5. 

Mortality, of measles, 301; of pella- 
gra, 310; rate of pellagra, in Cairo 
asylums, 33. 

Motion, uncertainty of, 255. 

Motor, disturbances, 149, 255, 264, 
309; excitement, 271; insufficiency 
of stomach, 216. 

Mount Vernon Hospital, 305. 

Mountain, countries, pellagra in, 
108; scurvy, 108, 

Multiple neuritis, 38. 

Murphy, J. G., 158. 

Muscular, atrophy, 230; progressive 
atrophy, 257; rigidity, 284; sense, 
256; tension, 255; weakness, 144, 
149, 249. 

Museum of North Carolina, 115. 

Myelitis, 250, 288; transverse, 257. 

Myxedematous infantilism, 128. 

Nails of fingers in pellagra, 171. 

Naples, Wollenburg's report on pella- 
gra from, 39. 

Nardi, 239, 260. 

Nascimbeni, 47. 

National Pellagra Conference, 34, 
310. 



Natural History of North Carolina, 
by John Brickell, M. D., 27. 

Neck, skin lesion of, 147. 

Negativism, 272. 

Negro, female, pellagra in, 122; in 
the South, 130. 

Nematode worms, a cause of pellagra, 
99. 

Nephritis, acute, 162; chronic inter- 
stitial, 306, 336. 

Nerves of skin in pellagra, 200. 

Nervous and mental manifestations 
of pellagra, 5, 208, 224. 

Nervous phenomena, 137, 138, 140, 
144, 286; depressive, 286. 

Nervous system, changes in, 120, 
147, 204. 

Nesbit, W. O., 215. 

Neuralgia, 250, 258. 

Neurasthenia, 137, 145, 250, 264, 285. 

Neuritic pains, 257. 

Neuritis, central, 241; descending, 
334; multiple, 38; parenchyma- 
tous, 240; peripheral, 251; post 
dysenteric, 38. 

Neuro-muscular excitement, 284. 

Neurotic symptoms, 258. 

Neusser, 92, 250. 

Neuwark, 251. 

New Jersey Hospital for the Insane, 
35. 

New Orleans, pellagra in, 131. 

New York Post-graduate Medical 
School, 30. 

Nicolas and Jambon, 9, 26. 

Niles, 215, 216, 218, 305. 

Noguchi reaction, 202, 228, 288. 

Non-pellagrous, children of pella- 
grous parents, 113; skin lesions, 
295. 

Non-transmissibility, 134. 

North Carolina, pellagra in, 33, 114, 
122, 123, 125, 132, 162, 170. 



INDEX 



369 



North Carolina Board of Charities, 

299. 
North Carolina Hospital for the 

Insane, 36. 
North Carolina Museum, 115. 
North Carolina State Board of 

Health, 36, 116. 
Nourishment, deficiency of, a cause 

of pellagra, 56; with spoilt maize, 

75. 
Noxiousness of corn, degree of, 95. 
Number of pellagrins in Italy, 40, 

41; in Tennessee, 44. 
Nutrition in pellagra, 346. 

Objective symptoms of pellagra, 
148. 

Obliteration of the central canal of 
the spinal cord, 228. 

Obscenity, 282. 

Obstetric features of pellagra, 157. 

Obstipation, 217. 

Occipital headache, 144. 

Odoardi, Jacobo, 9, 19, 50, 51, 52, 108, 
126, 131, 166. 

Odor of stools in pellagra, 221. 

Oidium lactis, 67, 69. 

Oil, of the embryo of spoilt maize, 
symptoms of, 82; of molded bread, 
symptoms of, 82; semidrying, a 
cause of pellagra (Mizell), 313. 

Oleoresin of spoilt corn, 67; three 
preparations from, 80. 

Olive oil, 118, 119. 

Onslow county, North Carolina, 
pellagra in, 115. 

Operative procedure in pellagra, 
310. 

Ophthalmic examination, 158; im- 
portance of, during atoxyl therapy, 
333, 334. 

Opisthotonus, 50, 260, 277. 

Optic nerve, effect of atoxyl on, 334; 



parenchymatous degeneration of, 

334. 
Order of appearance of symptoms, 

143, 150. 
Organism of spoilt corn, 83. 
Origin of pellagra, 2. 
Osier, Sir William, 1, 252, 254, 

301. 
Ottolenghi, 158. 

Over-conscientiousness, 275, 283. 
Oviedo, Casal a physician of, 7. 

Pachymeningitis, 228. 

Pain in pellagra, 255, 256, 348. 

Palms of hands in pellagra, 171. 

Papillae of tongue in pellagra, 145, 
162, 200, 258. 

Paradoxical contraction, of the ex- 
tensors of the foot, 137; of the 
flexors, 149. 

Parakeratosis, 201. 

Paralysis, 285. 

Paralytic gait, 256. 

Paralytic-spastic gait, 256. 

Paranoia, 149, 278. 

Paraparesis, spastic, 334. 

Paraplegia, 18. 

Parasitic, cause (animal) of pellagra, 
72; disease, 74, 97, 106, 114; 
infection in dogs, 75; intestinal 
infection, 126. 

Parenchymatous degeneration of cen- 
tral nervous system, 241; neuritis, 
240. 

Paresis, 137,249; circumscribed, 255; 
from pellagrosein, 78. 

Paresthesia, 147, 255, 257, 260, 
284. 

Paris, epidemic of (acrodynia), 18. 

Pathognomonic sign of pellagra, 107, 
146, 162, 258. 

Pathology, of the intestinal tract, 
217; of the nervous system, 35, 



370 



INDEX 



224; of the skin in pellagra, 199; 
of the spinal cord, 226. 

Paton, 279. 

Pectoral extension of the Casal 
collar, 166. 

Peculiarities of the Simulium, 117. 

Pelagia, 292. 

Pellagra, 292; areas of, 109; gaunt- 
let, 171; hemorrhagica, 196; in 
America, 29; in Andersonville 
prison, 28; in Asia, 30; in Austria, 
41, 108; in Bartonville Hospital, 
36; in children, 122, 128, 135, 167, 
344; in Cook County Hospital, 
36; in Georgia, 29; in Jamaica, 37; 
in Kansas, 117; in lower animals, 
77, 90; in the new-born, 128, 135; 
in Peoria State Hospital, 36; in 
South Carolina, 29; in Texas, 30; 
in those not eating maize, 103; in 
Turkestan, 30; in utero, 128; in 
well nourished, 83; in Wilmington, 
North Carolina, 34; mask, 176, 178, 
205; on banks of streams, 109; uni- 
versalis, 162, 308; with skin mani- 
festations, 142, 209. 

Pellagra-sine-pellagra, 127, 143, 146, 
161, 163, 209, 212, 242, 286, 309. 

Pellagrosari, 318. 

Pellagrosein, 65, 77, 79; effects of, 
on frogs, 78. 

Pellagrous, epilepsy, 277 ; manifesta- 
tions in dogs, 83; matter in cere- 
als, 93; paralysis, 277; spells, 
259. 

Pellarella, 2, 36. 

Pellarina in Pellano, 2, 19. 

Peltaub's animal experimentation, 
69. 

Pemphigus, 188; pellagrosus, 205. 

Penada, Jacobo, 56. 

Penicillium glaucum, 69, 96, 99. 

Peoria State Hospital, 120, 296. 



Peptonization of milk in pellagra, 
346. 

Perforation of intestinal ulcer, 219. 

Perhon and Papinian, 238. 

Perianal region, erythema of, 147, 
178. 

Pericardium, aspergillary infection 
of, 92, 186. 

Perineal region, erythema of, 147, 
198, 204. 

Period of incubation, 135. 

Peripheral neuritis, 251. 

Perivascular infiltration in pellagra, 
72. 

Peru, maize in, 102. 

Perugini, 328. 

Petechia? in stomach wall, 217. 

Pharyngeal reflex, 149. 

Phlegmasia of the liver, 11. 

Phobia, 264. 

"Phonemes," 273. 

Photophobia in chickens, 77. 

Pia mater, aspergillary infection of, 
92. 

Pianetta, 262. 

Piedmont section of North Carolina, 
pellagra in, 115. 

Pigeons, symptoms in, from pella- 
grosein, 79. 

Pigmentary disturbance of the skin, 
205. 

Pigmentation of the ganglion cells, 
228; of the papilla? of the tongue, 
145; of the skin, 146, 185, 193, 
195, 201. 

Placental infection of pellagra, 128. 

Plasmodium vivax, 106, 125. 

Pleura, aspergillary infection of, 92. 

Pleurosthotonic tetanus, 260. 

Pneumococcus of Frankel, resem- 
blance of, to the strepto-bacillus 
pellagra?, 86. 

Pneumonia, 124. 



INDEX 



371 



Points of predeliction of the skin in 

pellagra, 198. 
Poisoning, pellagrous, 61. 
Poland, pellagra in, 108. 
Polenta cultures, effect of, 70. 
Polyneuritis, 250, 257. 
Pompholix diurtinus, confusion of, 

with pellagra, 24. 
Portugal, pellagra in, 108. 
Possibility of pellagra in the lower 

animals, 90. 
Post dysenteric neuritis, 38. 
Posthumous work of Casal, 10. 
Potato bacillus, 68, 69, 85. 
Precis by C. H. Lavinder, 35. 
Predisposition, furnished by corn to 

the strepto-bacillus pellagrse, 88; 

to pellagra, 124, 130. 
Preerythematous stage of pellagra, 

144. 
Pregnancy, 123, 157. 
Premonitory symptoms, 135. 
Pressure in the head, 255. 
Prevalence of pellagra, in the United 

States, 46, 55, 60; on the banks 

of streams, 109. 
Prevention of the consumption of 

bad corn, 316. 
Prickling sensation, 255. 
Procopin, 35, 214, 255. 
Proctoclysis, 346. 
Prodromal stage, 136, 144. 
Prognosis, 271, 301, 330. 
Progressive paralysis, 261, 278. 
Properties of the strepto-bacillus 

pellagrse, 87. 
Prophylaxis, 56, 312, 318, 327; by 

Austrian Government, 42, 93. 
Protomedecin de Castille, 7. 
Protozoal, infection, 97, 160, 220; 

origin, 330, 331. 
Pruner, 46. 
Pseudo-general paralysis, 285. 



Pseudo-pellagra of Billod, 24, 26, 
61, 102, 103, 207, 292. 

Psilosis pigmentosa of Barbadoes, 
7, 27, 31, 32, 217. 

Psychasthenia, 265. 

Psychic, impediment, 277; irrita- 
bility, 144; symptoms, 148, 255. 

Psychical, catalepsy, 276; excita- 
bility, 278; irritability, 255. 

Psycho-motor, suspension, 273; re- 
tardation, 273, 284. 

Psycho-neurosis, 224. 

Psycho-physical weakness, congeni- 
tal, 127. 

Psychosis, 242; anxiety, 273; de- 
pressive, 263; intoxication, 273. 

Ptomaine poisoning, 71; produced 
by action on maize of micro-organ- 
isms, 71; produced by bacterium 
maidis, 71. 

Ptosis, unilateral, 250. 

Ptyalism, mercurial, -209. 

Pupillary disturbance in pellagra, 
261. 

Purpura, 196; chronica, 2, 6. 

Pustules in pellagra, 190, 192. 

Puyati, 9, 19, 47, 108. 

Pyrogenetic toxic substance in corn, 
75. 

Pyrosis in pellagra, 127, 214. 

Quarantine of pellagra, 133. 
Quarantino, 321. 

Quartan and tertian malaria, 125. 
Quinine in pellagra, 328. 

Race, proportions of, affected by 

pellagra, 122, 123. 
Ramazini, 52. 
Rampoldi, 159. 
Randi, 111. 

Randolph and Green, 239. 
Raphania maistica, 21. 



372 



INDEX 



Rarity of the Casal collar at the 
present time, 173. 

Rats, effect of pellagrosein on, 79; 
effects of spoilt corn on, 82. 

Raubitschek, 94. 

Rayer, 22. 

Raymond, 167, 170, 177, 200. 

Raynaud's disease, 244, 253. 

Reaction, electric, 256; of degenera- 
tion, 256. 

Receptive mother substance (Neus- 
ser), 91. 

Recommendations to Austrian Gov- 
ernment (prophylactic), 93. 

Recovery of atoxyl from the urine, 
332; time limit of, 147. 

Recrudescences of pellagra, 83, 193. 

Recurrences of erythema, 132, 146, 
147, 157, 198. 

Red oil of spoilt corn, 65; analogous 
to the oleoresin, 67. 

Redness of lips and tongue, 145; 
erythematous, 191. 

Reduction of pellagra in Italy 
(tables), 40. 

Reflexes, increase of, 147; lessening 
of, 147; pharyngeal, 149; skin, 
149; tendon, increase in, 75, 137, 
149, 284. 

Refusal of food, 75, 148, 277, 278. 

Regeneration of the horny layer of 
the skin, 189. 

Relapses, 74. 

Relationship of maize and pellagra, 99. 

Religious, ideas, 275; state (exalted), 
276. 

Removal of location, effect of, on 
pellagra, 307. 

Repetition of skin symptoms, 147. 

Requisites of hereditary transmis- 
sion, 127. 

Resemblance of pellagra and scor- 
butus, 49. 



Resinous substances of diseased corn, 

66, 67; character of, 66. 
Resistance of the strepto-bacillus 

pellagral to high temperature, 86; 

to treatment, 127. 
Rest in bed in treatment, 345. 
Restricted diet in pellagra, 346. 
Retardation, mental, 264. 
Retarded development of pellagra, 

127. 
Rete Malpighii in pellagra, 199, 200. 
Retinal changes from atoxyl, 334. 
Rhagades in pellagra, 190. 
Rhesus monkey, attempt to infect, 

with pellagra, 90, 134. 
Rheumatic fever, 124. 
Rhizopus, 75. 
Riggi, 240. 
Rigidity, 250; muscular, 137, 259; 

tetanic, 256. 
Rockefeller Commission for the Erad- 
ication of Hookworm Disease, 130, 

311. 
Rocky Mountain fever, 72, 113, 225. 
Rohrer, 238. 

Role of sunlight in etiology, 94. 
Romberg's sign, 260. 
Roncoroni, 215, 256. 
Ross, 251. 
Rossi, 237. 
Roumania, 108; pellagra in, 26, 37, 

41. 
Round cell perivascular infiltration 

in pellagra, 72. 
Round worms, 126, 138, 306. 
Roussel, 7, 8, 9, 17, 20, 54, 56, 59, 60, 

61, 133, 142, 145, 214, 220, 277. 
Rural, bakeries, 323; districts, pella- 
gra limited to, 106. 
Russia, pellagra in, 41. 

Saftzufuhr, 187. 
Saleris, 276. 



INDEX 



373 



Saliva of pellagrins, 134, 211. 
Salivary glands, 160, 211. 
Salivation, 146, 211, 286. 
Salt, a lack of, 51, 56; in treatment, 

328. 
Salvarsan, 341. 
Salvator vitale, 3. 
Sambon, L. W., 5, 36, 45, 50, 59, 72, 

92, 97, 100, 102, 104, 114, 124, 125, 

126, 127, 128, 133, 136, 150, 226, 

289, 312, 327; bodies, 289. 
SanareLli, 104. 
Sandfly theory, 117. 
Sandwith, 32, 33, 38, 46, 60, 135, 141, 

145, 211. 
Sanitary stations, 318. 
Saprophytic life of the strepto- 

bacillus pellagra?, 86. 
Sartago, 20, 47, 52, 108. 
Saunders, Eleanora B., 157. 
Sauvage, 4, 5, 9, 166. 
Savonarola, 100. 
Scalp, lesions of, 186. 
Scarlet fever, 46, 162, 210. 
Scliindler, 95. 
Sciatica, 250. 
Sclerosis, of pellagra, 238, 254; of 

vessels of the deeper layers of the 

skin, 199. 
Scheube, 136. 
Scorbutic pellagra, 6. 
Scorbuto alpino, 19; montano, 20. 
Scorbutus, differentiation of, from 

pellagra, 196. 
Scottatura di sole, 19. 
Scrotum, lesions of, 147. 
Scurvy, 1, 5, 46, 50. 
Searcy, G. H., 30, 86, 242, 302. 
Searcy, J. T., 30. 

Seasonal variations, 4, 106, 132, 206. 
Sebaceous glands in pellagra, 199. 
Secondary infection of the skin in 

pellagra, 188. 



Sectional peculiarities, 301. 

Self-condemnation, 282. 

Sennert, 46; ephelides of, 2. 

Sensation of cold, 148; of full uterus, 
148. 

Sensibility, anomalies of, 262; dis- 
turbance of, 256; loss of, 75. 

Sensitiveness, 265. 

Sensitized toxin in maize and rice, 
94. 

Septic poisoning, similarity of, to 
spoilt corn poisoning in the chick- 
en, 83. 

Serologic deviation of the comple- 
ment, 94. 

Serum, tests in pellagra, 161; therapy 
in pellagra, 349. 

Servia, pellagra in, 27, 108. 

Sette, Vincenzo, 52. 

Sex in peUagra, 122. 

Shell-like appearance of the erythema, 
196. 

Sherwell of Brooklyn, 29. 

Shetland Islands, pellagra in, 27. 

Shipping of maize, 68. 

Sicily, pellagra in, 103. 

Siler, 241, 263. 

Silver salts in pellagra, 347. 

Simulium, 312; inoculation of mon- 
keys by, 118; ornatum var. fascia- 
turn, 110; peculiarities of, 117; 
pubescens, 110; reptans, 5, 36, 97, 
106, 108, 112, 113, 117; vittatum, 
117. 

Sitophobia in dogs, 75, 214. 

Six hundred and six in treatment, 
342. 

Skin manifestations, 4, 5, 138, 145, 
161; character of, 183; in children, 
167; of arm, 171; of dogs, 72; re- 
flex, 149. 

Sleeping sickness, 97, 290. 

Sloan, H. N., 29. 



374 



INDEX 



Slowness, of ideas, 148; of move- 
ments after atoxyl, 334. 

Snow, 62. 

Soamin, 331, 333, 337. 

Solar, erythema, 184, 186, 202; influ- 
ence in the production of the ery- 
thema, 172, 204. 

Soler, 45, 52, 127. 

Sollicitudo, 3. 

Solsido, 6. 

Somato-physical degeneration in pel- 
lagra, 128. 

Sommerbrand, 3. 

Sound corn meal, study of, 83. 

South, labor situation in, 130. 

South Carolina, observers, 170; State 
Board of Health, 35. 

Spain, corn culture in, 58; pellagra 
in, 15, 108. 

Spaniards, introducers of maize, 100. 

Spanish pellagra, 8. 

Spasm, 334; of muscles, 260. 

Spastic gait,. 249, 260; paraplegia, 
334; spinal paralysis, 249. 

Specific, antitoxin against pellagra, 
91; cause of pellagra, 84; micro- 
organism of Tizzoni, 85. 

Speech, 150; disturbance of, 299. 

Spells, pellagrous, 259. 

Spesa, 52. 

Spiller, W. G., 251. 

Spinal cord, part affected, 147; 
in ergot, 226; in syphilis, 262. 

Spoilt corn, character of, 64. 

Sponginess of the gums, 209. 

Sporadic cases of pellagra, 113. 

Spore-bearing properties of the bac- 
terium maidis, 69. 

Sporisorium maidis, 61, 67. 

Spring recurrence, 4, 132. 

Sprue, 162, 212, 222, 287. 

Stage, 150; of cachexia, 149; of ery- 
thema, 144. 



Starvation, 148. 

Static ataxia, 149. 

Status lymphaticus, 303. 

Stefanowicz, 178. 

Stegomyia calopus, 107. 

Stelwagon, 297. 

Stephani, 111. 

.Stereotjrpies, 271; of motion, 270. 

Stigmata, 259. 

Stiles, Ch. Wardell, 28, 123, 130. 

Still births in Arabian pellagrins, 157. 

Stipple tongue, 145, 211. 

Stolid indifference, 264. 

Stomach in pellagra, 144, 215; con- 
tents of, 215; dilation of, 216; 
motor insufficiency of, 216. 

Stomatitis, 126, 145, 146, 148, 160, 
163, 191, 195, 204, 210, 286, 347; 
in amebic dysentery, 287; in men- 
tal disorders other than pellagra, 
263; materna, 214. 

Stools, in pellagra, 126; in sprue, 222. 

Storni, Dr., 47. 

Strachan, Henry, 37; disease, 38. 

Stratum, carneum, 200; granulosum 
in pellagra, 200. 

Strawberry tongue, 210. 

Streams and pellagra, 109. 

Strepto-bacillus pellagrae (Tizzoni), 
85, 91, 99, 2S7; in spoilt corn, 88; 
not the cause of pellagra, 91. 

Strombio, the elder, 2, 3, 4, 5, 6, 7, 9, 
19, 49, 50, 51, 52, 53, 61, 108, 126, 
133, 143, 144, 196, 208, 221, 224, 
239, 258, 313, 316, 351. 

Strombio, Gaetano, Junior, 94. 

Strychnine-like alkaloid of spoilt 
corn, 67, 83. 

Stupor, 241, 270, 271, 273, 277; 
affectless, 270. 

Substantia mater, 92. 

Subsultus, 259, 284, 309. 

Sudden death from pellagra, 302. 



INDEX 



375 



Suicide, 137, 148, 277, 302. 

Sun and pellagra, 53, 54, 162, 172. 

Sunlight, role of, in pellagra, 94, 309. 

Superiority of western maize, 74. 

Surgical procedure in pellagra, 157, 
310. 

Susceptibility to pellagra, 5; to pel- 
lagra, of lower animals, 77; to un- 
cinariasis, of negro, 123. 

Sweat glands in pellagra, 199, 200. 

Swiftly flowing streams and pellagra, 
113. 

Swooning, 277. 

Sydenham, 46. 

Symmetrical, erythema, 107, 120, 
146, 164, 185, 286; erythema other 
than pellagrous, 295; gangrene of 
the skin, 30, 262. 

Symmetry of the Casal collar, 172. 

Sympathetic system, abdominal 
changes in, 240. 

Symptoms, in monkeys after simu- 
lium inoculation, 118; of verdet 
poisoning, 61. 

Syphilis, 3, 107, 150, 183, 202, 214, 
224, 227, 288. 

Systematic monomania, 278. 

Tabes dorsalis, difference of, from pel- 
lagra, 236, 238. 

Table, of ages, 121; of blood and 
other changes in pellagra, 154, 156; 
of blood elements in various dis- 
eases, comparative, 153; of diseases 
predisposing to pellagra, 123; of 
sex, 122. 

Tactile, sense, 256, 260; stimuli, 
137, 259. 

Takacs, 42, 109. 

Tambourini, 103. 

Tanzi, 270, 271, 285. 

Tardy erythema, 164, 287. 

Tarzaglii, 47. 



Taylor, 345. 

Tendon reflex, increase in, 75, 149, 

260. 
Tennenbaum, 346. 
Tennessee, State Board of Health, 

36, 44, 122, 131, 132, 134; pellagra 

in, 44, 45, 123, 131. 
Tension,- muscular, 255. 
Terminations of pellagra, 120, 138. 
Tertian and quartan malaria, 125. 
Test meal in pellagra, 215. 
Tests, of Gosio, 59; of imported 

corn, 318; of spoilt corn, 64. 
Tetanic, state from pellagrosein, 78; 

movements, 259; rigidhVy, 256. 
Tetanus, 250, 259, 260, 277. 
Tetany, 149. 
Texas, pellagra in, 30. 
Thayer, W. S., 329. 
Theodori, Julius, 26, 145. 
Theories of etiology, 49. 
Thiery, 19. 
Thin of London, 31. 
Thighs, lesions of, 147, 186. 
Thinning, of epidermis in pellagra, 

200; of intestinal wall, 218. 
Thirst, 214. 

Thomas of Liverpool, 331. 
Thouvenel, 9, 21, 53, 56. 
Tincture of spoilt corn, composition 

of, 65. 
Tinnitus aurium, 148. 
Tinotti and Tedeschi, 237. 
Titius, 134. 

Tizzoni, 85, 86, 88, 99, 287. 
Tolerance, acquired, for the strepto- 

bacillus pellagrae, 88; of children, 

to pellagra, 92. 
Tongue in pellagra, 144, 145, 209, 210. 
Tonic, contraction of musculature, 

137, 149, 256; convulsions, 137; 

muscular spasm, 75; spasm, 259, 

260. 



376 



INDEX 



Topographical facts in pellagra, 97, 
106, 118. 

Torpor, cerebral, 75, 77; of muscles, 
75. 

Toxic, erythemata, 186; products of 
deteriorated maize, 72; pyrogene- 
tic substances in corn, 75; sub- 
stances from edible corn, 84, 
95. 

Toxicity, of atoxyl, 331; of penicil- 
lium, 96. 

Toxico-infective theory of pellagra, 
91. 

Townsend, Dr., an English traveller, 
10. 

Transfusion in pellagra, 348, 349. 

Transmissibility of pellagra, 133, 134; 
hereditary, 112. 

Transylvania, pellagra in, 42. 

Treatment, 327, 344; of diarrhoea, 
345; of skin lesions, 348; of 
stomatitis, 345. 

Tremor, muscular, 75, 137, 150, 309; 
of fingers, 260; of head and ton- 
gue, 149. 

Trevesan, pellagra in, 57. 

Trismus, 259. 

Tuczek, F., 34, 72, 148, 149, 217, 226, 
234, 236, 255, 256, 264. 

Turkestan, pellagra in, 30. 

Turkey, pellagra in, 108. 

Turkish wheat, 50, 57. See also 
Maize. 

Tyler, Dr., 29. 

Types of dessicators, 322; of pella- 
gra, 136, 141. 

Typhoid fever, 251; pellagra and, 85, 
136, 138, 139, 259, 271, 278, 284, 
310. See also Typhus pellagrosus. 

Typhus pellagrosus, 136, 150, 259, 
262, 271, 278, 284. 

Typical limitations of pellagra, 197. 

Tyrol, pellagra in, 27. 



Ulceration, of colon, 218; of ilium, 
218; of stomach, 217; of tongue, 
210. 

Ulcers of mouth, 145, 211. 

Umbria, pellagra in, 109. 

Uncertainty of motion, 144, 255. 

Uncinariasis, 27, 102, 123. 

Unexpected lesions, 147. 

United States, pellagra in, 46, 55, 60. 

Unusual localities of pellagrous skin 
lesions, 178. 

Urea, diminution, of, 157. 

Urine in pellagra, 156, 291. 

Urugua}^, pellagra in, 27. 

Uses of condemned corn, 75. 

Vaccination with the strepto-bacil- 
lus pellagra?, 88. 

Vaginitis, 157. 

Vales, Camara, 178. 

Vallc, Antonio del, 14. 

Van-der-Heuvell, 134. 

Variability in appearance of sjTnp- 
toms, 146; of pellagra returns, 305. 

Variations of the erythematous pro- 
cess, 292; of season on the pro- 
ducts of spoilt corn, SO. 

Vajr, 53. 

Vegetable diet in pellagra, 52. 

Verbigeration, 137, 222. 

Verderame, 25, 61. 

Verdet, 61. 

Verga, 222, 240, 262. 

Vertigo in pellagra, 107, 144, 148, 
258, 259, 2G4. 

Vesicles in the mouth, 145. 

Vesicular eczema, 296. 

Vesiculation of the buccal mucous 
membrane, 210. 

Videmar, 7, 134. 

Vienna, pellagra in, 26; report on 
pellagra from, 41. 

Villahoz, Perrote de, 17. 



INDEX 



377 



Violence, 282. 
Visual hallucination, 137. 
Vitiligo, 107, 202, 204. 
Vomiting, 145, 214, 216, 346. 
Von Scoccia, 196. 
Voracity in pellagra, 127, 215. 
Vulva, lesions of, 186. 
Vulvo-vaginitis, 157. 

Warnock, 32. 

Wasserman reaction, 161, 202, 228, 
288. 

Water, tendency to leap into, 255. 

Watson, J. J., 34, 157, 211, 215, 309. 

Weakness, 149; of lower extremi- 
ties, 255. 

Weather, and pellagra erythema, 198; 
effects of, on corn, 324. 

Weathered skin, differentiation of, 
from pellagra, 204. 

Weeping, 277. 

Weight, body, in pellagra, 351. 

Wellcome grant for the study of 
pellagra, 36. 



West Indies, Strachan's disease in, 
38. 

Wet skin lesions, 186, 190, 192. 

Whaley, 159. 

Whistler's thesis, 45. 

Whooping cough, 124. 

Williams, 25. 

Wilmington, North Carolina, pella- 
gra in, 34, 115. 

Wine, an absence of, as a cause, 56. 

Winthrop, G. J., 349. 

Wollenburg, 39. 

Worms, round, 126, 138, 306. 

Worth, W. E., on cotton seed oil, 119. 

Wright, J. B., 33. 

Wyman, Surgeon-General, 34. 

Zanetti, 50, 56. 
Zantedeschi, 60. 
Zecchinelli, 126, 134. 
Zeist, 57, 97, 123; school subdivi- 
sions of, 61. 
Zeitoxic school, 62. 
Zeller, 119, 173, 211, 296, 313. 



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